Allylic acetates derived from Baylis-Hillman reaction undergo efficient nucleophilic isomerization with imidazoles and triazoles to provide imidazolylmethyl and triazolylmethyl cinnamates stereoselectively. Antifungal evaluation of these derivatives against Cryptococcus neoformans exhibits good minimum inhibitory concentration values. These compounds exhibit low toxicity in proliferating MCF-7 breast cancer cell line. Structure activity relationship studies indicate that halogenated aromatic derivatives provide better antifungal activity.

Grady L. Nelson

Michael J. Williams

Shirisha Jonnalagadda

Mohammad A. Alam

Gautam Mereddy

Joseph L. Johnson

Sravan K. Jonnalagadda

Synthesis and Evaluation of Baylis-Hillman Reaction Derived Imidazole and Triazole Cinnamates as Antifungal Agents

X-ray and neutron crystallography are powerful techniques utilized to study the structures of biomolecules. Visualization of enzymes in complex with substrate/product and the capture of intermediate states can be related to activity to facilitate understanding of the catalytic mechanism. Subsequent analysis of small molecule binding within the enzyme active site provides insight into mechanisms of inhibition, supporting the design of novel inhibitors using a structure-guided approach. The first X-ray crystal structures were determined for small, ubiquitous enzymes such as carbonic anhydrase (CA). CAs are a family of zinc metalloenzymes that catalyze the hydration of CO2, producing <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.291101pt" id="M1" height="14.0878pt" version="1.1" viewBox="-0.0498162 -10.7967 39.3887 14.0878" width="39.3887pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g121-70" d="M729 650H468V622C546 615 554 610 554 527V365H213V527C213 610 221 616 297 622V650H38V622C120 616 128 611 128 527V123C128 39 120 34 40 28V0H303V28C221 34 213 40 213 123V322H554V123C554 39 546 34 460 28V0H728V28C647 34 639 39 639 123V527C639 610 647 615 729 622V650Z"/></g><g transform="matrix(.013,0,0,-0.013,9.801,0)"><path id="g121-65" 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><g transform="matrix(.013,0,0,-0.013,18.446,0)"><path id="g121-77" d="M381 665C170 665 44 498 44 318C44 125 188 -15 369 -15C552 -15 703 117 703 333C703 534 550 665 381 665ZM359 629C491 629 601 517 601 306C601 114 502 21 390 21C249 21 146 158 146 346S248 629 359 629Z"/></g><g transform="matrix(.0091,0,0,-0.0091,28.157,3.132)"><path id="g50-52" d="M290 377C321 398 342 415 358 430C378 450 389 473 389 502C389 578 329 635 238 635H237C184 635 137 610 109 578L64 515L88 493C112 529 154 573 208 573S303 542 303 482C303 409 233 370 141 341L149 308C165 313 190 319 215 319C272 319 341 283 341 193C342 98 292 43 222 43C163 43 122 72 96 94C88 101 79 100 70 94C61 87 47 73 46 60C44 47 48 37 62 23C76 10 118 -12 165 -12C238 -12 430 62 430 223C430 297 379 359 290 375V377Z"/></g><g transform="matrix(.0091,0,0,-0.0091,33.14,-5.741)"><path id="g54-33" d="M556 236V289H56V236H556Z"/></g></svg> and a proton. The CA structure and ping-pong mechanism have been extensively studied and are well understood. Though the function of CA plays an important role in a variety of physiological functions, CA has also been associated with diseases such as glaucoma, edema, epilepsy, obesity, and cancer and is therefore recognized as a drug target. In this review, a brief history of crystallography and its impact on CA research is discussed.

Carrie L. Lomelino

Jacob T. Andring

Robert McKenna

Crystallography and Its Impact on Carbonic Anhydrase Research

Some species of the Baccharis genus have been shown to possess important biomedical properties, including cytotoxic activity. In this study, we examined the cytotoxic effect of methanol extract from Baccharis obtusifolia (Asteraceae) in cancer cell lines of prostate (PC-3), colon (RKO), astrocytoma (D-384), and breast (MCF-7). The methanolic extract displayed the largest substantial cytotoxic effect in lines of colon cancer (RKO) and cerebral astrocytoma (D-384). Chromatographic purification of the B. obtusifolia methanolic extract led to the isolation and identification of 5,4&#x2032;-dihydroxy-7-methoxyflavone (1) and 5-hydroxy-7,4&#x2032;-dimethoxyflavone (2) compounds of the flavonoid type.

Juan Carlos Romero-Benavides

Gina C. Ortega-Torres

Javier Villacis

Sara L. Vivanco-Jaramillo

Karla I. Galarza-Urgil&#xe9;s

Natalia Bailon-Moscoso

Phytochemical Study and Evaluation of the Cytotoxic Properties of Methanolic Extract from Baccharis obtusifolia

Acquired Immunodeficiency Syndrome (AIDS) has been devastating for millions of people around the world. Inhibition of the human immunodeficiency virus (HIV) protease is among the most important approaches for the therapeutic intervention in HIV infection. Since the discovery of the HIV-1 protease, this enzyme has been considered as a key target for the inhibition of viral replication. A large body of research has been done to develop an effective HIV-1 protease inhibitor. There are to date 10 HIV-1 protease inhibitor drugs approved by the Food and Drug Administration (FDA) that have improved the survival and quality of life of HIV infected people. These drugs are prescribed in combination with the reverse transcriptase inhibitors, which is referred to as highly active antiretroviral therapy (HAART). The HIV-1 protease inhibitors play a vital role in HAART. The applications of click chemistry are dispersing in the field of drug discovery. Recently, click chemistry has captured a lot of attention and has become a powerful tool for the synthesis of medicinal skeletons in the discovery of anti-HIV drugs. Click reaction is a well-known method for making carbon&#x2212;heteroatom&#x2212;carbon bonds. Click reactions are popular because they are wide in scope, of high yielding, quick to perform, and easy to purify. In this review, we outlined current approaches towards the development of HIV-1 protease inhibitors employing click chemistry.

Mukesh M. Mudgal

Nagaraju Birudukota

Mayur A. Doke

Applications of Click Chemistry in the Development of HIV Protease Inhibitors

Carbonic anhydrases (CAs) are thought to be important for regulating pH in the tumor microenvironment. A few of the CA isoforms are upregulated in cancer cells, with only limited expression in normal cells. For these reasons, there is interest in developing inhibitors that target these tumor-associated CA isoforms, with increased efficacy but limited nonspecific cytotoxicity. Here we present some of the biophysical, biochemical, and cell based techniques and approaches that can be used to evaluate the potency of CA targeted inhibitors and decipher the role of CAs in tumorigenesis, cancer progression, and metastatic processes. These techniques include esterase activity assays, stop flow kinetics, and mass inlet mass spectroscopy (MIMS), all of which measure enzymatic activity of purified protein, in the presence or absence of inhibitors. Also discussed is the application of X-ray crystallography and Cryo-EM as well as other structure-based techniques and thermal shift assays to the studies of CA structure and function. Further, large-scale genomic and proteomic analytical methods, as well as cell based techniques like those that measure cell growth, apoptosis, clonogenicity, and cell migration and invasion, are discussed. We conclude by reviewing approaches that test the metastatic potential of CAs and how the aforementioned techniques have contributed to the field of CA cancer research.

Mam Y. Mboge

Anusha Kota

Susan C. Frost

Biophysical, Biochemical, and Cell Based Approaches Used to Decipher the Role of Carbonic Anhydrases in Cancer and to Evaluate the Potency of Targeted Inhibitors

The design, synthesis, and development of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are respectable area of research. Novel Diclofenac Schiff&#x2019;s bases (M1, M2, M4, M7, and M8) were designed and synthesized, and their respective chemical structures were deduced using various spectral tools (IR, 1H NMR, 13C NMR, and MS). The compounds were synthesized via Schiff&#x2019;s condensation reaction and their anti-inflammatory activity was investigated applying the Carrageenan-induced paw edema model against Diclofenac as positive control. Percentage inhibition of edema indicated that all compounds were exhibiting a comparable anti-inflammatory activity as Diclofenac. Moreover, the anti-inflammatory activity was supported via virtual screening using molecular docking study. Interestingly compound M2 showed the highest in vivo activity (61.32&#x25; inhibition) when compared to standard Diclofenac (51.36&#x25; inhibition) as well as the best binding energy score (-10.765) and the virtual screening docking score (-12.142).

Musab Mohamed Ibrahim

Tilal Elsaman

Mosab Yahya Al-Nour

Synthesis, Anti-Inflammatory Activity, and In Silico Study of Novel Diclofenac and Isatin Conjugates

A new trisazo dye has been synthesized by coupling the diazonium ion of 3-amino-4H thieno[3,4-c][1]benzopyran-4-one with 2-tert-butyl-4-methoxyphenol. The newly prepared trisazo dye was characterized by its physical, elemental, and spectroscopic data. 2D-NMR (COSY, HSQC, and HMBC) techniques were used to secure the structural assignments. The new trisazo dye (compound 7) along with precursors 3, 4, and 6 was screened by microdilution susceptibility assay for antibacterial and antifungal activities towards eight bacterial strains and three yeasts selected on the basis of their relevance as human pathogens. The results showed that compound 7 (MIC = 2&#x2013;128&#x2009;&#x3bc;g/mL) was the most active as compared with its precursors. The most resistant microorganisms were V. cholerae NB2 and V. cholerae SG24, whereas the most sensitive microorganism was C. neoformans. The overall results of this study indicated that compound 7 had the greatest potential value against both yeasts and multidrug-resistant bacteria, so further investigation is warranted.

Joseph Tsemeugne

Emmanuel Sopbu&#xe9; Fondjo

Jean-de-Dieu Tamokou

Taoufik Rohand

Arnaud Djintchui Ngongang

Jules Roger Kuiate

Beibam Luc Sondengam

Synthesis, Characterization, and Antimicrobial Activity of a Novel Trisazo Dye from 3-Amino-4H-thieno[3,4-c][1]benzopyran-4-one

Rescoring is a simple approach that theoretically could improve the original docking results. In this study AutoDock Vina was used as a docked engine and three other scoring functions besides the original scoring function, Vina, as well as their combinations as consensus scoring functions were employed to explore the effect of rescoring on virtual screenings that had been done on diverse targets. Rescoring by DrugScore produces the most number of cases with significant changes in screening power. Thus, the DrugScore results were used to build a simple model based on two binding site descriptors that could predict possible improvement by DrugScore rescoring. Furthermore, generally the screening power of all rescoring approach as well as original AutoDock Vina docking results correlated with the Maximum Theoretical Shape Complementarity (MTSC) and Maximum Distance from Center of Mass and all Alpha spheres (MDCMA). Therefore, it was suggested that, with a more complete set of binding site descriptors, it could be possible to find robust relationship between binding site descriptors and response to certain molecular docking programs and scoring functions. The results could be helpful for future researches aiming to do a virtual screening using AutoDock Vina and/or rescoring using DrugScore.

Jamal Shamsara

Correlation between Virtual Screening Performance and Binding Site Descriptors of Protein Targets

About this journal

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.

Journal profile

Meet the editorial board

International Journal of Medicinal Chemistry maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.

Editor spotlight

Submit your proposal

Do you think there is an emerging area of research that really needs to be highlighted? Or an existing research area that has been overlooked or would benefit from deeper investigation? Raise the profile of a research area by leading a Special Issue.

Special Issues

Author guidelines

Editorial board

Databases and indexing

International Journal of Medicinal Chemistry - Table of contents 2018

International Journal of Medicinal Chemistry | Hindawi

title

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

description

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.

https://images.hindawi.com/journals/ijmc/ijmc.banner.jpg

International Journal of Medicinal Chemistry