http://www.hindawi.comThe latest articles from Hindawi Publishing Corporation© 2012, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/826792/An optimized synthetic route to prepare ring-locked retinoid 1a has been developed. We fully describe a purification protocol that provides isomerically pure 1a in support of on-going proof of concept studies for the development of therapeutic agents to treat human ADRP. Additionally, we have found that isomerically pure 1a can be stored in amber vials under argon at −20°C for use over time (up to six months) without degradation. Thus, enabling 1a to be an accessible and valuable biological tool.Jamie B. Côté, Tan D. Quach, Andrey P. Demenev, David S. Garvey, and Judd M. BermanCopyright © 2011 Jamie B. Côté et al. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/678101/α-Aminophosphonates are bioisosteres of amino acids and have several pharmacological activities. These compounds have been synthesized by various routes from reaction between amine, aldehyde, and phosphite compounds. In order to synthesize α-aminophosphonates, catalytic effect of CuCl2 was compared with FeCl3. Also all designed structures as well as griseofulvin were docked into the active site of microtubule (1JFF), using Autodock program. The results showed that the reactions were carried out in the presence of CuCl2 in lower yields, and also the time of reaction was longer in comparison with FeCl3. The chemical structures of the new compounds were confirmed by spectral analyses. The compounds were investigated for antifungal activity against several fungi in comparison with griseofulvin. An indole-derived bis(α-aminophosphonates) with the best negative ΔG in docking study showed maximum antifungal activity against Microsporum canis, and other investigated compounds did not have a good antifungal activity.Zahra Rezaei, Soghra Khabnadideh, Kamiar Zomorodian, Keyvan Pakshir, Setareh Nadali, Nadia Mohtashami, and Ehsan Faghih MirzaeiCopyright © 2011 Zahra Rezaei et al. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/403039/Parkinson's disease (PD) is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic) neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa) significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS). In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist.Shin Hisahara and Shun ShimohamaCopyright © 2011 Shin Hisahara and Shun Shimohama. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/648960/The neonatal ventral hippocampal lesion (nVHL) has been widely used as an animal model for schizophrenia. Rats with an nVHL show several delayed behavioral alterations that mimic some symptoms of schizophrenia. Sprague-Dawley (SD) rats with an nVHL have a decrease in D3 receptors in limbic areas, but the expression of D3 receptors in Wistar (W) rats with an nVHL is unknown. The 7-Hydroxy-2-(N,N-di-n-propylamino) tetralin (7-OH-DPAT) has been reported as a D3-preferring agonist. Thus, we investigated the effect of (±)-7-OH-DPAT (0.25 mg/kg) on the motor activity in male adult W and SD rats after an nVHL. The 7-OH-DPAT caused a decrease in locomotion of W rats with an nVHL, but it did not change the locomotion of SD rats with this lesion. Our results suggest that the differential effect of 7-OH-DPAT between W and SD rats with an nVHL could be caused by a different expression of the D3 receptors. These results may have implications for modeling interactions of genetic and environmental factors involved in schizophrenia.Sonia Guzmán-Velázquez, Linda Garcés-Ramírez, Gonzalo Flores, Fidel De La Cruz, and Sergio R. ZamudioCopyright © 2011 Sonia Guzmán-Velázquez et al. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/424535/The novel selective D1 dopaminergic full agonists A-68930, A-77636 were discovered by the synthesis of molecules to probe the bioactive conformation of the partial agonist SKF-38393, by the use of this information to add D1 affinity and selectivity to a screening hit, and by traditional medicinal chemistry exploration of structure-activity relationships. The subsequent design of A-86929 and ABT-413 capitalized on these results, recently disclosed agonists, and traditional medicinal chemistry.Yvonne Connolly MartinCopyright © 2011 Yvonne Connolly Martin. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/480652/In the past few decades, medicinal chemistry research towards potent and selective antagonists of human adenosine receptors (namely, A1, A2A, A2B, and A3) has been evolving rapidly. These antagonists are deemed therapeutically beneficial in several pathological conditions including neurological and renal disorders, cancer, inflammation, and glaucoma. Up to this point, many classes of compounds have been successfully synthesized and identified as potent human adenosine receptor antagonists. In this paper, an overview of the structure-activity relationship (SAR) profiles of promising nonxanthine pyrazolo derivatives is reported and discussed. We have emphasized the SAR for some representative structures such as pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidines; pyrazolo-[3,4-c] or -[4,3-c]quinolines; pyrazolo-[4,3-d]pyrimidinones; pyrazolo-[3,4-d]pyrimidines and pyrazolo-[1,5-a]pyridines. This overview not only clarifies the structural requirements deemed essential for affinity towards individual adenosine receptor subtypes, but it also sheds light on the rational design and optimization of existing structural templates to allow us to conceive new, more potent adenosine receptor antagonists.Siew Lee Cheong, Gopalakrishnan Venkatesan, Priyankar Paira, Ramasamy Jothibasu, Alexander Laurence Mandel, Stephanie Federico, Giampiero Spalluto, and Giorgia PastorinCopyright © 2011 Siew Lee Cheong et al. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/592879/From well-known antioxidants agents, we developed a first pharmacophore model containing four common chemical features: one aromatic ring and three hydrogen bond acceptors. This model served as a template in virtual screening of Maybridge and NCI databases that resulted in selection of sixteen compounds. The selected compounds showed a good antioxidant activity measured by three chemical tests: DPPH radical, OH∘ radical, and superoxide radical scavenging. New synthetic compounds with a good correlation with the model were prepared, and some of them presented a good antioxidant activity.Mustapha El Bakkali, Lhassane Ismaili, Isabelle Tomassoli, Laurence Nicod, Marc Pudlo, and Bernard RefouveletCopyright © 2011 Mustapha El Bakkali et al. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/253962/Curcuma zedoaria belonging to the family Zingiberaceae has been used in the traditional system of medicine in India and Southwest Asia in treating many human ailments and is found to possess many biological activities. The rationale of the present study was to isolate, identify, and characterize antitumour principles from the rhizomes of Curcuma zedoaria, to assess its cytotoxic effects on human and murine cancer cells, to determine its apoptosis inducing capacity in cancer cells, and to evaluate its tumour reducing properties in in vivo mice models. Isocurcumenol was characterized as the active compound by spectroscopy and was found to inhibit the proliferation of cancer cells without inducing significant toxicity to the normal cells. Fluorescent staining exhibited the morphological features of apoptosis in the compound-treated cancer cells. In vivo tumour reduction studies revealed that a dose of 35.7 mg/kg body weight significantly reduced the ascitic tumour in DLA-challenged mice and increased the lifespan with respect to untreated control mice.S. Lakshmi, G. Padmaja, and P. RemaniCopyright © 2011 S. Lakshmi et al. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/562421/Two series of fused tetrahydro-β-carboline hydantoin and tetrahydro-β-carboline thiohydantoin derivatives with a pendant 2,4-dimethoxyphenyl at position 5 were synthesized, and chiral carbons at positions 5 and 11a swing from R,R to R,S, S,R, and S,S. The prepared analogues were evaluated for their capacity to inhibit phosphodiesterase 5 (PDE5) isozyme. The R absolute configuration of C-5 in the β-carboline hydantoin derivatives was found to be essential for the PDE5 inhibition. Chiral carbon derived from amino acid even if of the S configuration (L-tryptophan) may lead to equiactive or more active isomers than those derived from amino acid with the R configuration (D-tryptophan). This expands the horizon from which efficient PDE5 inhibitors can be derived and may offer an economic advantage. The thiohydantoin derivatives were less active than their hydantoin congeners.Ashraf H. Abadi, Jochen Lehmann, Gary A. Piazza, Mohammad Abdel-Halim, and Mohamed S. M. AliCopyright © 2011 Ashraf H. Abadi et al. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/530780/Based on the structure of three previously established lead compounds, fifteen selected chalcones were synthesized and evaluated for their multidrug resistance (MDR) reversal activity on mouse lymphoma cells. The most active chalcones were stronger revertants than the positive control, verapamil. In the model of combination chemotherapy, the interactions between the anticancer drug doxorubicin and two of the most effective compounds were measured in vitro, on human MDR1 gene transfected mouse lymphoma cells, showing that the type of interaction for one of these compounds was indifferent while that for the other one was additive. Furthermore, two chalcones inhibited 50% of cell proliferation in concentration of around 0.4 μg/mL and were from 2- to 100-fold more active than the most chalcones. The structure-activity relationships were obtained and discussed in view of their usefulness for the design of chalcone-like P-gp modulators and drugs able to treat resistant cancers.A. B. Ivanova, D. I. Batovska, I. T. Todorova, B. A. Stamboliyska, J. Serly, and J. MolnarCopyright © 2011 A. B. Ivanova et al. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/539245/Identification of selective influenza viral sialidase inhibitors is highly desirable in order to minimize or avoid the adverse effects due to the possible inhibition of endogenous human sialidases. We recently reported the evaluation of C9 N-acyl Neu5Ac2en mimetics as probes for human sialidases. Herein, we describe the in vitro activity of the same set of C9 N-acyl Neu5Ac2en mimetics against sialidases expressed by influenza virus A/PR/8/34 (H1N1), A/Memphis/1/72 (H3N2), and A/Duck/313/78 (H5N3) strains. Compound 8 is identified as a promising starting point for the development of viral sialidase selective inhibitors. Multiple sequence alignment and molecular docking techniques are also performed to explore the plausible interaction of compound 8 with viral sialidases.Sadagopan Magesh, Nongluk Sriwilaijaroen, Setsuko Moriya, Hiromune Ando, Taeko Miyagi, Yasuo Suzuki, Hideharu Ishida, and Makoto KisoCopyright © 2011 Sadagopan Magesh et al. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/213135/Many viral pathogens encode the motor proteins named RNA helicases which display various functions in genome replication. General strategies to design specific and selective drugs targeting helicase for the treatment of viral infections could act via one or more of the following mechanisms: inhibition of the NTPase activity, by interferences with ATP binding and therefore by limiting the energy required for the unwinding and translocation, or by allosteric mechanism and therefore by stabilizing the conformation of the enzyme in low helicase activity state; inhibition of nucleic acids binding to the helicase; inhibition of coupling of ATP hydrolysis to unwinding; inhibition of unwinding by sterically blocking helicase translocation. Recently, by in vitro screening studies, it has been reported that several benzotriazole, imidazole, imidazodiazepine, phenothiazine, quinoline, anthracycline, triphenylmethane, tropolone, pyrrole, acridone, small peptide, and Bananin derivatives are endowed with helicase inhibition of pathogen viruses belonging to Flaviviridae, Coronaviridae, and Picornaviridae families.Irene Briguglio, Sandra Piras, Paola Corona, and Antonio CartaCopyright © 2011 Irene Briguglio et al. All rights reserved.http://www.hindawi.com/journals/ijmc/2011/918168/We investigated the 16α-hydroxylation of steroid molecules and regioselective binding mode in homology-modeled cytochrome P450-2C11 to correlate the biological study with the computational molecular modeling. It revealed that there was a positive relationship between the observed inhibitory potencies and the binding free energies. Docking of steroid molecules into this homology-modeled CYP2C11 indicated that 16α-hydroxylation is favored with steroidal molecules possessing the following components, (1) a bent A-B ring configuration (5β-reduced), (2) C-3 α-hydroxyl group, (3) C-17β-acetyl group, and (4) methyl group at both the C-18 and C-19. These respective steroid components requirements were defined as the inhibitory contribution factor. Overall studies of the male rat CYP2C11 metabolism revealed that the above-mentioned steroid components requirements were essential to induce an effective inhibition of [3H]progesterone 16α-hydroxylation. As far as docking of homology-modeled CYP2C11 against investigated steroids is concerned, they are docked at the active site superimposed with flurbiprofen. It was also found that the distance between heme iron and C16α-H was between 4 to 6 Å and that the related angle was in the range of 180±45∘.Hamed I. Ali, Morio Yamada, Yukihisa Fujita, Mitsuko Maeda, and Eiichi AkahoCopyright © 2011 Hamed I. Ali et al. All rights reserved.