International Journal of Medicinal Chemistry The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Synthesis and Biological Evaluation of Aminonaphthols Incorporated Indole Derivatives Wed, 10 Sep 2014 00:00:00 +0000 An efficient one pot condensation of naphthols (1), 2,5-disubstituted indole-3-carboxaldehydes (2), and secondary amines (3) has been achieved using dichloromethane as a solvent, stirring at room temperature. Some of the new [(disubstituted amino)(5-substituted 2-phenyl-1H-indol-3-yl)methyl]naphthalene-ols (4) derivatives were prepared in good yields. The significant features of this method are simple work-up procedure, inexpensive nontoxic solvent, shorter reaction times, and excellent product yields. The structures of newly synthesized compounds (4a–r) are confirmed by their elemental analysis, FTIR, 1H and 13C NMR, and mass spectral data. These compounds were screened for their in vitro antioxidant, antimicrobial, antitubercular, and anticancer activities. Among the synthesized compounds (4a–r), the compound 4e exhibited highest activity for radical scavenging and ferric ions reducing antioxidant power activities; compounds 4b, 4h, and 4k showed good metal chelating activity. Compounds 4n and 4q showed excellent antimicrobial activities with MIC value 08 µg/mL against tested strains. Compounds 4h, 4k, 4n, and 4q exhibited promising antitubercular activity with MIC value 12.5 µg/mL. Compounds 4k and 4q exhibited 100% cell lysis at concentration 10 µg/mL against MDA-MB-231 (human adenocarcinoma mammary gland) cell lines. Saundane Anand Raghunath and Kirankumar Nandibeoor Mathada Copyright © 2014 Saundane Anand Raghunath and Kirankumar Nandibeoor Mathada. All rights reserved. Docking Studies and Biological Activity of Fosinopril Analogs Sun, 06 Jul 2014 06:48:37 +0000 The purpose of the present study was to determine the angiotensin-I converting enzyme inhibitory activity of few novel Fosinopril derivatives which were predicted to possess better ACE inhibitory activity and lesser side effects than the existing drug molecule. In vitro study was carried out to determine ACE inhibitory activity of six different Fosinopril analogs by spectrophotometric assay procedure. Analog A2 showed the highest activity compared to other analogs and as well as Fosinopril itself. Docking studies of the compounds were done with the help of VLife MDS 3.0 software using GRIP batch docking method to find out which derivative had a better docking with ACE. The compounds which showed the highest negative score in docking have also exhibited good ACE inhibitory activity. Jayant Choudary, Suvarna G. Kini, Sreedhara Ranganath Pai Karkala, and Muhammad Mubeen Copyright © 2014 Jayant Choudary et al. All rights reserved. Target Based Designing of Anthracenone Derivatives as Tubulin Polymerization Inhibiting Agents: 3D QSAR and Docking Approach Thu, 17 Apr 2014 10:54:08 +0000 Novel anthracenone derivatives were designed through in silico studies including 3D QSAR, pharmacophore mapping, and molecular docking approaches. Tubulin protein was explored for the residues imperative for activity by analyzing the binding pattern of colchicine and selected compounds of anthracenone derivatives in the active domain. The docking methodology applied in the study was first validated by comparative evaluation of the predicted and experimental inhibitory activity. Furthermore, the essential features responsible for the activity were established by carrying out pharmacophore mapping studies. 3D QSAR studies were carried out for a series of 1,5- and 1,8-disubstituted10-benzylidene-10H-anthracen-9-ones and 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-one derivatives for their antiproliferation activity. Based on the pattern recognition studies obtained from QSAR results, ten novel compounds were designed and docked in the active domain of tubulin protein. One of the novel designed compounds “N1” exhibited binding energy −9.69 kcal/mol and predicted Ki 78.32 nM which was found to be better than colchicine. Abdul Samad, Moawiah M. Naffaa, Mohammed Afroz Bakht, Manav Malhotra, and Majid A. Ganaie Copyright © 2014 Abdul Samad et al. All rights reserved. Significance and Biological Importance of Pyrimidine in the Microbial World Sun, 23 Mar 2014 12:34:34 +0000 Microbes are unique creatures that adapt to varying lifestyles and environment resistance in extreme or adverse conditions. The genetic architecture of microbe may bear a significant signature not only in the sequences position, but also in the lifestyle to which it is adapted. It becomes a challenge for the society to find new chemical entities which can treat microbial infections. The present review aims to focus on account of important chemical moiety, that is, pyrimidine and its various derivatives as antimicrobial agents. In the current studies we represent more than 200 pyrimidines as antimicrobial agents with different mono-, di-, tri-, and tetrasubstituted classes along with in vitro antimicrobial activities of pyrimidines derivatives which can facilitate the development of more potent and effective antimicrobial agents. Vinita Sharma, Nitin Chitranshi, and Ajay Kumar Agarwal Copyright © 2014 Vinita Sharma et al. All rights reserved. A Novel Inhibitor of Mammalian Triosephosphate Isomerase Found by an In Silico Approach Sun, 23 Mar 2014 09:34:20 +0000 Triosephosphate isomerase (TIM) is an essential, highly conserved component of glycolysis. Tumors are often dependent on glycolysis for energy and metabolite production (the Warburg effect). Glycolysis inhibitors thus show promise as cancer treatments. TIM inhibition, unlike inhibition of other glycolysis enzymes, also produces toxic methylglyoxal targeted to regions of high glycolysis, an effect that might also be therapeutically useful. Thus TIM is an attractive drug target. A total of 338,562 lead-like molecules were analyzed computationally to find TIM inhibitors by an efficient “double screen” approach. The first fragment-sized compounds were studied using structure-based virtual screening to identify binding motifs for mammalian TIM. Subsequently, larger compounds, filtered to meet the binding criteria developed in the first analysis, were ranked using a second round of structure-based virtual screening. A compound was found that inhibited mammalian TIM in vitro in the micromolar range. Docking and molecular dynamics (MD) suggested that the inhibitor made hydrogen bond contacts with TIM catalytic residues. In addition, hydrophobic contacts were made throughout the binding site. All predicted inhibitor-TIM interactions involved TIM residues that were highly conserved. The discovered compound may provide a scaffold for elaboration of other inhibitors. Lorraine Marsh and Kaushal Shah Copyright © 2014 Lorraine Marsh and Kaushal Shah. All rights reserved. Experimental Design-Based Response Surface Methodology Optimization for Synthesis of β-Mercapto Carbonyl Derivatives as Antimycobacterial Drugs Catalyzed by Calcium Pyrophosphate Thu, 06 Mar 2014 11:09:10 +0000 A simple protocol for the efficient preparation of β-mercapto carbonyl derivatives as antimycobacterial drugs has been achieved via Thia-Michael reaction between chalcones derivatives and thiols in the presence of calcium pyrophosphate as a heterogeneous catalyst under mild reaction conditions. The central composite design was used to design an experimental program to provide data to model the effects of various factors on reaction yield . The variables chosen were catalyst weight , reaction time , and solvent volume . The mathematical relationship of reaction yield on the three significant independent variables can be approximated by a nonlinear polynomial model. Predicted values were found to be in good agreement with experimental values. The optimum reaction conditions for reaction model (chalcone and thiophenol) obtained by response surface were applied to other substrates. This procedure provides several advantages such as high yield, clean product formation, and short reaction time. Younes Abrouki, Abdelkader Anouzla, Hayat Loukili, Jamal Bennazha, Rabiaâ Lotfi, Ahmed Rayadh, My Abdellah Bahlaoui, Saïd Sebti, Driss Zakarya, and Mohamed Zahouily Copyright © 2014 Younes Abrouki et al. All rights reserved. Therapeutic Potential of Hydrazones as Anti-Inflammatory Agents Tue, 04 Mar 2014 09:06:24 +0000 Hydrazones are a special class of organic compounds in the Schiff base family. Hydrazones constitute a versatile compound of organic class having basic structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities. Hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal, anti-HIV, and so forth. The present review summarizes the efficiency of hydrazones as potent anti-inflammatory agents. Anu Kajal, Suman Bala, Neha Sharma, Sunil Kamboj, and Vipin Saini Copyright © 2014 Anu Kajal et al. All rights reserved. Clicked Cinnamic/Caffeic Esters and Amides as Radical Scavengers and 5-Lipoxygenase Inhibitors Tue, 18 Feb 2014 10:29:38 +0000 5-Lipoxygenase (5-LO) is the key enzyme responsible for the conversion of arachidonic acid to leukotrienes, a class of lipid mediators implicated in inflammatory disorders. In this paper, we describe the design, synthesis, and preliminary activity studies of novel clicked caffeic esters and amides as radical scavengers and 5-LO inhibitors. From known 5-LO inhibitor 3 as a lead, cinnamic esters 8a–h and amides 9a–h as well as caffeic esters 15a–h and amides 16a–h were synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloaddition with the appropriate azide precursors and terminal alkynes. All caffeic analogs are proved to be good radical scavengers (IC50: 10–20 μM). Esters 15g and 15f possessed excellent 5-LO inhibition activity in HEK293 cells and were equipotent with the known 5-LO inhibitor CAPE and more potent than Zileuton. Several synthesized esters possess activities rivaling Zileuton in stimulated human polymorphonuclear leukocytes. Jérémie A. Doiron, Benoît Métayer, Ryan R. Richard, Dany Desjardins, Luc H. Boudreau, Natalie A. Levesque, Jacques Jean-François, Samuel J. Poirier, Marc E. Surette, and Mohamed Touaibia Copyright © 2014 Jérémie A. Doiron et al. All rights reserved. Abrus precatorius Leaves: Antioxidant Activity in Food and Biological Systems, pH, and Temperature Stability Thu, 30 Jan 2014 00:00:00 +0000 Natural antioxidants present in foods and other biological materials have attracted considerable interest because of their presumed safety and potential nutritional and therapeutic effects. Antioxidant constituents of plant materials act as radical scavengers and convert the radicals to less reactive species. Abrus precatorius (AP) was analyzed for its proximate and phytochemical composition. The leaves were extracted with methanol (ME) and analyzed for antioxidant activity by radical scavenging method, reducing power, ferric reducing capacity, and in vitro inhibition of Fenton’s reagent-induced oxidation in oil emulsion and microsomes. In addition, the effect of temperature (, 15, and 30 min) and pH (4.5, 7, and 9) C on the antioxidant activity of ME was investigated. The leaves were rich in total polyphenols, flavonoids, β-carotene, glutathione, α-tocopherol, and ascorbic acid. The ME exhibited varying degree of antioxidant activity in a dose-dependent manner. The AP exhibited more inhibition of oxidation in microsomes (73%) than compared to oil emulsion (21%). Heat treatment resulted in an increase of radical scavenging activity of extract (28% to 43%). At pH 4.5 the extract exhibited more antioxidant activity and stability compared to pH 7 and 9. Data indicates that potential exists for the utilization of Abrus precatorius as a natural antioxidant. Vanitha Reddy Palvai, Sowmya Mahalingu, and Asna Urooj Copyright © 2014 Vanitha Reddy Palvai et al. All rights reserved. Estimation of Anti-HIV Activity of HEPT Analogues Using MLR, ANN, and SVM Techniques Mon, 30 Dec 2013 08:57:17 +0000 The present study deals with the estimation of the anti-HIV activity of a large set of 107 HEPT analogues using molecular descriptors which are responsible for the anti-HIV activity. The study has been undertaken by three techniques MLR, ANN, and SVM. The MLR model fits the train set with while in ANN and SVM with higher values of , respectively. SVM model shows improvement to estimate the anti-HIV activity of trained data, while in test set ANN have higher value than those of MLR and SVM techniques. metrics and ridge regression analysis indicated that the proposed four-variable model MATS5e, RDF080u, T(O⋯O), and MATS5m as correlating descriptors is the best for estimating the anti-HIV activity (log 1/C) present set of compounds. Basheerulla Shaik, Tabassum Zafar, and Vijay K. Agrawal Copyright © 2013 Basheerulla Shaik et al. All rights reserved. Synthesis of N-(6-(4-(Piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide Derivatives for the Treatment of Metabolic Syndrome Mon, 23 Dec 2013 10:40:04 +0000 Metabolic syndrome is a widely prevalent multifactorial disorder associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. High plasma levels of insulin and glucose due to insulin resistance are a major component of the metabolic disorder. Thiazolidinediones (TZDs) are potent PPARγ ligand and used as insulin sensitizers in the treatment of type 2 diabetes mellitus. They are potent insulin-sensitizing agents but due to adverse effects like hepatotoxicity, a safer alternative of TZDs is highly demanded. Here we report synthesis of N-(6-(4-(piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide derivatives as an alternate remedy for insulin resistance. Nabajyoti Deka, Swapnil Bajare, Jessy Anthony, Amrutha Nair, Anagha Damre, Dharmeshkumar Patel, Chandrika B-Rao, H. Sivaramakrishnan, Shivaprakash Jagalur Mutt, Chandan Wilankar, and Rosalind Marita Copyright © 2013 Nabajyoti Deka et al. All rights reserved. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens Wed, 27 Nov 2013 10:35:30 +0000 The three-dimensional (3D) structures of human leukocyte antigen (HLA) molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures. Shinji Amari, Ryoichi Kataoka, Takashi Ikegami, and Noriaki Hirayama Copyright © 2013 Shinji Amari et al. All rights reserved. Synthesis and Evaluation of Some Novel Chromone Based Dithiazoles as Antimicrobial Agents Wed, 27 Nov 2013 10:29:32 +0000 Novel substituted 1,2,4-dithiazolylchromones 3a–j were synthesized by the reaction of 3-formylchromones (1a–j) with two equivalents of p-chlorothiobenzamide (2) in dry xylene and characterized spectroscopically (IR, 1H and 13C NMR, mass) and elemental analysis. All synthesized compounds were screened for in vitro antimicrobial activity against various pathogenic bacterial and fungal strains and were found to possess good to moderate inhibitory potential against all tested strains. Antimicrobial results reveal that compounds bearing lipophilic electron withdrawing groups such as chloro and bromo displayed significant inhibitory potential against both bacterial and fungal strains. Particularly, compound 3c displayed significant inhibitory against bacterial strains and compound 3h exhibits significant inhibitory potential in comparison to standard drug fluconazole against fungal strain S. cerevisiae. Naureen Aggarwal, Vishal Sharma, Harpreet Kaur, and Mohan Paul Singh Ishar Copyright © 2013 Naureen Aggarwal et al. All rights reserved. Synthesis Characterization and Antibacterial, Antifungal Activity of N-(Benzyl Carbamoyl or Carbamothioyl)-2-hydroxy Substituted Benzamide and 2-Benzyl Amino-Substituted Benzoxazines Thu, 31 Oct 2013 13:28:05 +0000 New N-(benzyl carbamothioyl)-2-hydroxy substituted benzamides 13, 20, and 21 were synthesized using sodium bicarbonate and benzyl amine with 2-thioxo-substituted-1,3-benzoxazines 6, 10a, b, 11c, and 12a–n. The 2-thioxo-substituted-1,3-oxazines 6, 10a-b, 11d 12a–n, and 26 were converted to the corresponding 2-methylthio-substituted-1,3-oxazines 14a–l and 24 which were then converted to 2-benzyl amino-substituted-benzoxazines 15a–i by refluxing with benzylamine. Products 15a, b, e, f, and g were also synthesized by boiling the corresponding N-(benzyl carbamothioyl)-2-hydroxy substituted benzamides 13a, b, f, l, and m in acetic acid. 2-Oxo-substituted-1,3-benzoxazines 22 and 25 were prepared by treating the corresponding 2-methylthio-substituted-1,3-oxazines 14 and 24 with dilute HCl. The N-(benzyl carbamoyl)-2-hydroxy substituted benzamide 23 was synthesized from the reaction of 2-oxo-substituted-1,3-benzoxazine 22 with benzylamine. The new products were characterized using IR, 1H, and 13C NMR in addition to microanalysis. Selected compounds were tested in vitro for antibacterial and antifungi activity and the most active compounds were found to be the 4-(substituted-benzylamino)-2-hydroxy benzoic acids 9a and d (M. chlorophenolicum, MIC 50 and 25 µgm L−1, resp.), N1, N3-bis (benzyl carbamothioyl)-4,6-dihydroxy-substituted phthalamides 20a and 20c (B. subtilis MIC 12.5, 50 µgm L−1, resp.) and 21 (M. chlorophenolicum, MIC 50 µgm L−1). Tyson Belz, Saleh Ihmaid, Jasim Al-Rawi, and Steve Petrovski Copyright © 2013 Tyson Belz et al. All rights reserved. Novel Antimicrobial Agents: Fluorinated 2-(3-(Benzofuran-2-yl) pyrazol-1-yl)thiazoles Wed, 11 Sep 2013 11:06:21 +0000 A new series of 2-pyrazolin-1-ylthiazoles 8a–d and 13–16 was synthesized by cyclization of N-thiocarboxamide-2-pyrazoline with different haloketones and 2,3-dichloroquinoxaline. The structures of the new compounds were confirmed by elemental analyses as well as NMR, IR, and mass spectral data. The newly synthesized compounds were evaluated for their antimicrobial activities, and also their minimum inhibitory concentration (MIC) against most of test organisms was performed. Amongst the tested ones, compound 8c displayed excellent antimicrobial activity. Hanan A. Mohamed, Ehab Abdel-Latif, Bakr F. Abdel-Wahab, and Ghada E. A. Awad Copyright © 2013 Hanan A. Mohamed et al. All rights reserved. Computational Study of Estrogen Receptor-Alpha Antagonist with Three-Dimensional Quantitative Structure-Activity Relationship, Support Vector Regression, and Linear Regression Methods Tue, 14 May 2013 15:46:06 +0000 Human estrogen receptor (ER) isoforms, ERα and ERβ, have long been an important focus in the field of biology. To better understand the structural features associated with the binding of ERα ligands to ERα and modulate their function, several QSAR models, including CoMFA, CoMSIA, SVR, and LR methods, have been employed to predict the inhibitory activity of 68 raloxifene derivatives. In the SVR and LR modeling, 11 descriptors were selected through feature ranking and sequential feature addition/deletion to generate equations to predict the inhibitory activity toward ERα. Among four descriptors that constantly appear in various generated equations, two agree with CoMFA and CoMSIA steric fields and another two can be correlated to a calculated electrostatic potential of ERα. Ying-Hsin Chang, Jun-Yan Chen, Chiou-Yi Hor, Yu-Chung Chuang, Chang-Biau Yang, and Chia-Ning Yang Copyright © 2013 Ying-Hsin Chang et al. All rights reserved. Recent Pharmacological Developments on Rhodanines and 2,4-Thiazolidinediones Thu, 02 May 2013 09:07:53 +0000 Thiazolidines are five-member heterocyclic having sulfur, nitrogen, and oxygen atoms in their ring structure and exhibiting potent as well as wide range of pharmacological activities. In this minireview, recent updates on synthesis and pharmacological evaluations of molecules based on 2,4-thiazolidine and rhodanine are discussed. Ravinder Singh Bhatti, Sakshi Shah, Suresh, Pawan Krishan, and Jagir S. Sandhu Copyright © 2013 Ravinder Singh Bhatti et al. All rights reserved. Synthetic Methods, Chemistry, and the Anticonvulsant Activity of Thiadiazoles Tue, 30 Apr 2013 14:42:38 +0000 The chemistry of heterocyclic compounds has been an interesting field of study for a long time. Heterocyclic nucleus 1,3,4-thiadiazole constitutes an important class of compounds for new drug development. The synthesis of novel thiadiazole derivatives and investigation of their chemical and biological behavior have gained more importance in recent decades. The search for antiepileptic compounds with more selective activity and lower toxicity continues to be an active area of intensive investigation in medicinal chemistry. During the recent years, there has been intense investigation of different classes of thiadiazole compounds, many of which possess extensive pharmacological activities, namely, antimicrobial activity, anticonvulsant, antifungal antidiabetic, anti-inflammatory, antioxidant, and antituberculosis activities, and so forth. The resistance towards available drugs is rapidly becoming a major worldwide problem. The need to design new compounds to deal with this resistance has become one of the most important areas of research today. Thiadiazole is a versatile moiety that exhibits a wide variety of biological activities. Thiadiazole moiety acts as “hydrogen binding domain” and “two-electron donor system.” It also acts as a constrained pharmacophore. On the basis of the reported literature, we study here thiadiazole compounds and their synthetic methods chemistry and anticonvulsant activity. Bhawna Sharma, Amita Verma, Sunil Prajapati, and Upendra Kumar Sharma Copyright © 2013 Bhawna Sharma et al. All rights reserved. Microwave-Assisted Synthesis and Biological Evaluation of Dihydropyrimidinone Derivatives as Anti-Inflammatory, Antibacterial, and Antifungal Agents Mon, 15 Apr 2013 18:27:17 +0000 A simple protocol for the efficient preparation of aryl and heteroaryl substituted dihydropyrimidinone has been achieved via initial Knoevenagel, subsequent addition, and final cyclization of aldehyde, ethylcyanoacetate, and guanidine nitrate in the presence of piperidine as a catalyst in solvent-free under microwave irradiation. The synthesized compounds showed a good anti-inflammatory, antibacterial, and antifungal activity. Anjna Bhatewara, Srinivasa Rao Jetti, Tanuja Kadre, Pradeep Paliwal, and Shubha Jain Copyright © 2013 Anjna Bhatewara et al. All rights reserved. A Possible Molecular Mechanism of Immunomodulatory Activity of Bilirubin Tue, 09 Apr 2013 15:59:45 +0000 Bilirubin is an endogenous product of heme degradation in mammals. Bilirubin has long been considered as a cytotoxic waste product that needs to be excreted. However, increasing evidence suggests that bilirubin possesses multiple biological activities. In particular, recent studies have shown that bilirubin should be a protective factor for several autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. Since these autoimmune diseases are closely associated with specific types of human leukocyte antigens (HLAs), we have hypothesized that bilirubin might bind to the antigenic peptide-binding groove of the HLA molecules and exert its immunosuppressive actions. In order to evaluate the hypothesis, theoretical docking studies between bilirubin and the relevant HLA molecules have been undertaken. The in silico studies have clearly shown that bilirubin may bind to the antigenic peptide-binding groove of the HLA molecules relevant to the autoimmune diseases with significant affinity. The bound bilirubin may block the binding of antigenic peptides to be presented to T cell receptors and lead to suppression of the autoimmune responses. Based on this hypothesis new drug discovery research for autoimmune diseases will be conducted. Hideto Isogai and Noriaki Hirayama Copyright © 2013 Hideto Isogai and Noriaki Hirayama. All rights reserved. Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors Thu, 04 Apr 2013 14:07:06 +0000 DHEA, 17α-AED, 17β-AED, and 17β-AET exhibit strong biological activity that has been attributed to androgenic, estrogenic, or antiglucocorticoid activity in vivo and in vitro. This study compared DHEA, 17α-AED, 17β-AED, and 17β-AET for their ability to activate the human AR, ER, and GR and determine the relative androgenicity, estrogenicity, and glucocorticoid activity. The results show that, at the receptor level, these androstene hormones are weak AR and even weaker ER activators. Direct androstene hormone activation of the human AR, ERα, and ERβ may not be essential for their biological function. Similarly, these hormones indirectly activated the human GR, only in the presence of high dexamethasone concentrations. These results underscore the major difference between androstene hormone interactions with these nuclear receptors and their biological effects. Thomas L. Shaak, Dayanjan S. Wijesinghe, Charles E. Chalfant, Robert F. Diegelmann, Kevin R. Ward, and Roger M. Loria Copyright © 2013 Thomas L. Shaak et al. All rights reserved. Synthesis and In Vitro Antimicrobial Evaluation of New 1,3,4-Oxadiazoles Bearing 5-Chloro-2-methoxyphenyl Moiety Sun, 31 Mar 2013 16:11:26 +0000 A series of new 1,3,4-oxadiazole derivatives, 4(a–h), containing 5-chloro-2-methoxy benzohydrazide moiety were synthesized by the reaction of 5-chloro-2-methoxybenzoate with different aromatic carboxylic acids. These newly synthesized compounds were characterized by FT-IR, 1H NMR, mass spectra, and also by elemental analysis. All the newly synthesized compounds were screened for their antibacterial and antifungal activities. Antimicrobial studies revealed that compounds 4c, 4f, and 4g showed significant activity against tested strains. Basavapatna N. Prasanna Kumar, Kikkeri N. Mohana, Lingappa Mallesha, and Kikkeri P. Harish Copyright © 2013 Basavapatna N. Prasanna Kumar et al. All rights reserved. The Development of Models Based on Linear and Nonlinear Multivariate Methods to Predict ADME/PK Properties Using Physicochemical Properties of Kinase, Protease Inhibitors, and GPCR Antagonists Tue, 19 Mar 2013 12:08:40 +0000 Oral bioavailability of a drug compound is the significant property for potential drug candidates. Measuring this property can be costly and time-consuming. Quantitative structure-property relationships (QSPRs) are used to estimate the percentage of oral bioavailability, and they are an attractive alternative to experimental measurements. A data set of 217 drug and drug-like compounds with measured values of the percentage of oral bioavailability taken from the small molecule ChemBioBase database was used to develop and test a QSPR model. Descriptors were calculated for the compounds using Codessa 2.1 tool. Nonlinear general regression neural network model was generated using the DTREG predictive modeling program software. The calculated percentage of oral bioavailability model performs well, with root-mean-square (rms) errors of 4.55% oral bioavailability units for the training set, 14.32% oral bioavailability units for the test set, and 19.12% oral bioavailability units for the external prediction set. Given the structural diversity and bias of the data set, this is a good first attempt at modeling oral bioavailability using QSPR methods. The model can be used as a potential virtual screen or property estimator. With a larger data supply less biased toward the high end values of the percentage of oral bioavailability, a more successful model could likely be developed. Deepu Bakasta and M. G. Shambhu Copyright © 2013 Deepu Bakasta and M. G. Shambhu. All rights reserved. Synthesis and Anticancer Properties of Silver(I) Complexes Containing 2,6-Bis(substituted)pyridine Derivatives Tue, 05 Mar 2013 13:46:27 +0000 Several new 2,6-bis(substituted)pyridine ligands and 2,6-bis(substituted)pyridine Ag(I) nitrate complexes were synthesized and characterized spectroscopically. The newly synthesized ligands include pyridine-2,6-bis(3-oxopropanenitrile) (1), pyridine-2,6-bis(2-cyano-N-phenyl-3-oxopropanethioamide) (2), and pyridine-2,6-bis((E)-2-(2-phenylhydrazono)-3-oxopropanenitrile) (3). The newly synthesized ligands and silver(I) complexes were evaluated for their in vitro anticancer activity against four human cancer cell lines including hepatocellular carcinoma (HePG2), lung adenocarcinoma (A549), colon carcinoma (HT29), and breast adenocarcinoma (MCF7). Most of the newly synthesized silver(I) complexes exhibited better activity than the ligands, and the results have been compared with doxorubicin as a reference drug. Korany A. Ali, Mokhles M. Abd-Elzaher, and Khaled Mahmoud Copyright © 2013 Korany A. Ali et al. All rights reserved. Catalyst-Free Synthesis of Highly Biologically Active 5-Arylidene Rhodanine and 2,4-Thiazolidinedione Derivatives Using Aldonitrones in Polyethylene Glycol Thu, 14 Feb 2013 15:00:23 +0000 A green, efficient synthesis of 5-arylidene rhodanine and 2,4-thiazolidinedione derivatives without using any external catalyst in polyethylene glycol (PEG) at 80°C has been described. Reaction procedure is very simple, short, and obtained yields are very high. Dhruva Kumar, Suresh Narwal, and Jagir S. Sandhu Copyright © 2013 Dhruva Kumar et al. All rights reserved. Synthesis and In Vitro Cytotoxic Activity of Chromenopyridones Tue, 08 Jan 2013 15:42:10 +0000 Novel substituted chromenopyridones (3a–j and 6a–d) were synthesized and evaluated in vitro for the cytotoxic activity against various human cancer cell lines such as prostate (PC-3), breast (MCF-7), CNS (IMR-32), cervix (Hela), and liver (Hep-G2). preliminary cytotoxic screening showed that all the compounds possess a good to moderate inhibitory activity against various cancer cell lines. Particularly, compound 6b bearing allyl moiety displayed a significant cytotoxic potential in comparison to standard drugs. Balwinder Singh, Vishal Sharma, Gagandeep Singh, Rakesh Kumar, Saroj Arora, and Mohan Paul Singh Ishar Copyright © 2013 Balwinder Singh et al. All rights reserved. Secondary Structural Preferences of Some Antibacterial Cyclooctapeptides in the Presence of Calcium(II) Tue, 18 Dec 2012 10:29:37 +0000 The purpose of this study is to understand the interactions of some antibacterial cationic amphipathic cyclooctapeptides with calcium(II) and their secondary structural preferences. The thermodynamic parameters associated with calcium(II) interactions, between the antibacterial active cyclooctapeptides (COP 1–6) and those that did not exhibit significant activities (COP 7–9), were studied by isothermal titration calorimetry. Calcium(II) binding in the absence and presence of micellar dodecylphosphocholine (DPC), a membrane mimicking detergent, was conducted by circular dichroism (CD). Both groups of cyclopeptides showed weak binding affinities for calcium(II) (Kb ca. 10−3 M−1). However, CD data showed that the antimicrobial peptides COP 1–6 adopted a twisted beta-sheet structure (positive CD absorption band at ca. 203 nm) in the presence of calcium(II) in micellar DPC. In contrast, COP 7–9, which lacked antibacterial activity, adopted a different conformational structure (negative CD absorption band at ca. 203 nm). These results indicate that these cyclopeptides could adopt secondary structural preferences in the presence of calcium(II) amidst a hydrophobic environment to elicit their antibacterial activity. These findings could be useful in facilitating the design of cyclopeptide derivatives that can adopt this beta-sheet-like secondary structure and, thereby, provide a useful molecular template for crafting antibacterial compounds. Tarshona Stevens, Nykia McNeil, Xiuli Lin, and Maria Ngu-Schwemlein Copyright © 2012 Tarshona Stevens et al. All rights reserved. A DFT and Semiempirical Model-Based Study of Opioid Receptor Affinity and Selectivity in a Group of Molecules with a Morphine Structural Core Tue, 18 Dec 2012 09:47:32 +0000 We report the results of a search for model-based relationships between mu, delta, and kappa opioid receptor binding affinity and molecular structure for a group of molecules having in common a morphine structural core. The wave functions and local reactivity indices were obtained at the ZINDO/1 and B3LYP/6-31 levels of theory for comparison. New developments in the expression for the drug-receptor interaction energy expression allowed several local atomic reactivity indices to be included, such as local electronic chemical potential, local hardness, and local electrophilicity. These indices, together with a new proposal for the ordering of the independent variables, were incorporated in the statistical study. We found and discussed several statistically significant relationships for mu, delta, and kappa opioid receptor binding affinity at both levels of theory. Some of the new local reactivity indices incorporated in the theory appear in several equations for the first time in the history of model-based equations. Interaction pharmacophores were generated for mu, delta, and kappa receptors. We discuss possible differences regulating binding and selectivity in opioid receptor subtypes. This study, contrarily to the statistically backed ones, is able to provide a microscopic insight of the mechanisms involved in the binding process. Tamara Bruna-Larenas and Juan S. Gómez-Jeria Copyright © 2012 Tamara Bruna-Larenas and Juan S. Gómez-Jeria. All rights reserved. Synthesis, Characterization, and Biological Evaluation of Some New Functionalized Terphenyl Derivatives Thu, 13 Dec 2012 15:25:19 +0000 New functionalized terphenyl derivatives incorporating various heterocyclic rings are prepared by using 4,4′′-difluoro-5′-hydroxy-1,1′:3′,1′′-terphenyl-4′-carbohydrazide as a key intermediate derived from 4,4′-difluoro chalcone, a versatile synthone. All the derivatives are characterized by 1H NMR, IR, and mass spectral data. All the synthesized products are screened for their in vitro antimicrobial and antioxidant properties. The majority of the tested compounds exhibited significant antioxidant activity and some of them showed good antimicrobial activity. Seranthimata Samshuddin, Badiadka Narayana, Balladka Kunhanna Sarojini, Divya N. Shetty, and Nalilu Suchetha Kumari Copyright © 2012 Seranthimata Samshuddin et al. All rights reserved. In Silico Inhibition Studies of Jun-Fos-DNA Complex Formation by Curcumin Derivatives Thu, 06 Dec 2012 09:25:35 +0000 Activator protein-1 (AP1) is a transcription factor that consists of the Jun and Fos family proteins. It regulates gene expression in response to a variety of stimuli and controls cellular processes including proliferation, transformation, inflammation, and innate immune responses. AP1 binds specifically to 12-O-tetradecanoylphorbol-13-acetate (TPA) responsive element 5′-TGAG/CTCA-3′ (AP1 site). It has been found constitutively active in breast, ovarian, cervical, and lung cancers. Numerous studies have shown that inhibition of AP1 could be a promising strategy for cancer therapeutic applications. The present in silico study provides insights into the inhibition of Jun-Fos-DNA complex formation by curcumin derivatives. These derivatives interact with the amino acid residues like Arg155 and Arg158 which play a key role in binding of Jun-Fos complex to DNA (AP1 site). Ala151, Ala275, Leu283, and Ile286 were the residues present at binding site which could contribute to hydrophobic contacts with inhibitor molecules. Curcumin sulphate was predicted to be the most potent inhibitor amongst all the natural curcumin derivatives docked. Anil Kumar and Utpal Bora Copyright © 2012 Anil Kumar and Utpal Bora. All rights reserved.