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

Ajay Kumar Agarwal

Significance and Biological Importance of Pyrimidine in the Microbial World

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 &#x201C;double screen&#x201D; 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

Kaushal Shah

A Novel Inhibitor of Mammalian Triosephosphate Isomerase Found by an In Silico Approach

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 <svg style="vertical-align:-2.3205pt;width:23.424999px;" id="M1" height="15.0875" version="1.1" viewBox="0 0 23.424999 15.0875" width="23.424999" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,12.138)"><path id="x28" d="M300 -147l-18 -23q-106 71 -159 185.5t-53 254.5v1q0 139 53 252.5t159 186.5l18 -24q-74 -62 -115.5 -173.5t-41.5 -242.5q0 -130 41.5 -242.5t115.5 -174.5z" /></g><g transform="matrix(.017,-0,0,-.017,5.944,12.138)"><path id="x1D44C" d="M667 650l-9 -28q-53 -5 -76 -17t-64 -59q-51 -61 -175 -225q-21 -29 -27 -55l-27 -136q-13 -65 -0.5 -80t83.5 -22l-7 -28h-280l8 28q64 4 81 19t30 83l25 128q6 35 -7 65l-98 231q-17 41 -32.5 52t-68.5 16l8 28h252l-6 -28l-40 -4q-27 -3 -33 -12.5t2 -31.5&#xA;q8 -26 43 -107.5t61 -134.5q114 145 174 240q14 24 8 33t-37 13l-34 4l8 28h238z" /></g><g transform="matrix(.017,-0,0,-.017,17.486,12.138)"><path id="x29" d="M275 270q0 -296 -211 -440l-19 23q75 62 116.5 174t41.5 243t-42 243t-116 173l19 24q211 -144 211 -440z" /></g></svg>. The variables chosen were catalyst weight <svg style="vertical-align:-3.276pt;width:31.6875px;" id="M2" height="16.275" version="1.1" viewBox="0 0 31.6875 16.275" width="31.6875" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,12.137)"><use xlink:href="#x28" /></g><g transform="matrix(.017,-0,0,-.017,5.944,12.137)"><path id="x1D44B" d="M775 650l-6 -28q-60 -6 -81.5 -16t-61.5 -54l-175 -191l125 -243q30 -58 48.5 -71t82.5 -19l-5 -28h-275l7 28l35 4q31 4 37 12t-6 34l-108 216q-140 -165 -177 -219q-16 -22 -10.5 -30.5t41.5 -13.5l22 -3l-7 -28h-244l8 28q52 4 75 15.5t67 52.5q48 46 206 231&#xA;l-110 215q-26 51 -44 63t-72 17l6 28h250l-6 -28l-27 -4q-30 -5 -35 -10t3 -27q17 -43 95 -190q70 78 154 185q15 21 10 29.5t-33 12.5l-30 4l5 28h236z" /></g><g transform="matrix(.012,-0,0,-.012,19.412,16.212)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" /></g><g transform="matrix(.017,-0,0,-.017,25.738,12.137)"><use xlink:href="#x29" /></g></svg>, reaction time <svg style="vertical-align:-3.276pt;width:31.6875px;" id="M3" height="16.275" version="1.1" viewBox="0 0 31.6875 16.275" width="31.6875" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,12.137)"><use xlink:href="#x28" /></g><g transform="matrix(.017,-0,0,-.017,5.944,12.137)"><use xlink:href="#x1D44B" /></g><g transform="matrix(.012,-0,0,-.012,19.412,16.212)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g><g transform="matrix(.017,-0,0,-.017,25.738,12.137)"><use xlink:href="#x29" /></g></svg>, and solvent volume <svg style="vertical-align:-3.39066pt;width:31.6875px;" id="M4" height="16.4125" version="1.1" viewBox="0 0 31.6875 16.4125" width="31.6875" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,12.138)"><use xlink:href="#x28" /></g><g transform="matrix(.017,-0,0,-.017,5.944,12.138)"><use xlink:href="#x1D44B" /></g><g transform="matrix(.012,-0,0,-.012,19.412,16.212)"><path id="x33" d="M285 378v-2q65 -13 102 -54.5t37 -97.5q0 -57 -30.5 -104.5t-74 -75t-85.5 -42t-72 -14.5q-31 0 -59.5 11t-40.5 23q-19 18 -16 36q1 16 23 33q13 10 24 0q58 -51 124 -51q55 0 88 40t33 112q0 64 -39 96.5t-88 32.5q-29 0 -64 -11l-6 29q77 25 118 57.5t41 84.5&#xA;q0 45 -26.5 69.5t-68.5 24.5q-67 0 -120 -79l-20 20l43 63q51 56 127 56h1q66 0 107 -37t41 -95q0 -42 -31 -71q-22 -23 -68 -54z" /></g><g transform="matrix(.017,-0,0,-.017,25.738,12.138)"><use xlink:href="#x29" /></g></svg>. 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

Rabia&#xe2; Lotfi

Ahmed Rayadh

My Abdellah Bahlaoui

Sa&#xef;d Sebti

Driss Zakarya

Mohamed Zahouily

Experimental Design-Based Response Surface Methodology Optimization for Synthesis of &#x3b2;-Mercapto Carbonyl Derivatives as Antimycobacterial Drugs Catalyzed by Calcium Pyrophosphate

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

Vipin Saini

Therapeutic Potential of Hydrazones as Anti-Inflammatory Agents

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&#x2013;h and amides 9a&#x2013;h as well as caffeic esters 15a&#x2013;h and amides 16a&#x2013;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&#x2013;20&#x2009;&#x3BC;M). 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.

J&#xe9;r&#xe9;mie A. Doiron

Beno&#xee;t M&#xe9;tayer

Ryan R. Richard

Dany Desjardins

Luc H. Boudreau

Natalie A. Levesque

Jacques Jean-Fran&#xe7;ois

Samuel J. Poirier

Marc E. Surette

Mohamed Touaibia

Clicked Cinnamic/Caffeic Esters and Amides as Radical Scavengers and 5-Lipoxygenase Inhibitors

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.&#x2009;&#x2009;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&#x2019;s reagent-induced oxidation in oil emulsion and microsomes. In addition, the effect of temperature (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2325001pt" id="M1" height="11.1597pt" version="1.1" viewBox="-0.0498162 -10.9272 31.8561 11.1597" width="31.8561pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g50-50" d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z"/></g><g transform="matrix(.013,0,0,-0.013,6.331,0)"><path id="g50-49" d="M245 635C92 635 37 457 37 312C37 149 91 -12 244 -12C395 -12 449 166 449 312C449 469 395 635 245 635ZM243 598C332 598 358 454 358 312C358 173 334 26 245 26C158 26 128 174 128 313S152 598 243 598Z"/></g><g transform="matrix(.013,0,0,-0.013,12.662,0)"><use xlink:href="#g50-49"/></g><g transform="matrix(.0091,0,0,-0.0091,19.064,-5.872)"><path id="g54-73" d="M339 262C339 340 273 403 193 403S48 340 48 262S113 121 193 121S339 184 339 262ZM283 262C283 210 242 168 193 168S104 210 104 262S144 356 193 356S283 314 283 262Z"/></g><g transform="matrix(.013,0,0,-0.013,23.079,0)"><path id="g190-68" d="M614 175C564 76 510 21 408 21C256 21 146 149 146 336C146 488 235 629 402 629C510 629 570 586 597 480L626 488C620 541 614 582 606 638C578 643 510 665 429 665C206 665 44 527 44 316C44 157 153 -15 402 -15C474 -15 558 5 586 11C604 45 629 119 643 165L614 175Z"/></g></svg>, 15, and 30&#x2009;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, &#x3b2;-carotene, glutathione, &#x3b1;-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&#x25;) than compared to oil emulsion (21&#x25;). Heat treatment resulted in an increase of radical scavenging activity of extract (28&#x25; to 43&#x25;). 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

Asna Urooj

Abrus precatorius Leaves: Antioxidant Activity in Food and Biological Systems, pH, and Temperature Stability

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International Journal of Medicinal Chemistry ceased publication in 2020 and is no longer accepting submissions.

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International Journal of Medicinal Chemistry

International Journal of Medicinal Chemistry publishes original research articles as well as review articles in all areas of chemistry associated with drug discovery, design, and synthesis.

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International Journal of Medicinal Chemistry