ABSTRACT
A series of novel N-(3-aryl-1,2,4-triazol-5-yl) cinnamamide derivatives were designed on basis of structural similarity to the known FAS II inhibitors. Topliss operational method was used to optimize the potency of molecules. The minimum inhibitory concentration (MIC) of all synthesized compounds was determined against Mycobacterium tuberculosis H(37)R(v) using resazurin microtitre assay (REMA) plate method. The synthesized compounds exhibit antimycobacterial activity in the range of 5-95µM with a good safety profile.
Subject(s)
Amides/chemistry , Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Cinnamates/chemical synthesis , Cinnamates/pharmacology , Mycobacterium tuberculosis/drug effects , Antitubercular Agents/chemistry , Cinnamates/chemistry , Drug Evaluation, Preclinical , Humans , Microbial Sensitivity TestsABSTRACT
A series of cinnamide derivatives was designed as potential antimycobacterial agents using molecular hybridization approach. The diamine moiety, a key feature of ethambutol and its other analogs, and certain structural features of cerulenin and cinnamic acid were hybridized to obtain cinnamide derivatives. The minimum inhibitory concentration (MIC) of all synthesized compounds was determined against M. tuberculosis H(37)R(v) using Resazurin Microtitre plate Assay (REMA) method. The synthesized molecules showed good to moderate activity with MIC in the range of 5-150 µM and good safety profile. Additionally, the most potent compound 1a, having MIC 5.1 µM exhibited synergy with rifampicin.
Subject(s)
Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Cinnamates/chemistry , Cinnamates/pharmacology , Mycobacterium/drug effects , Animals , Antitubercular Agents/chemical synthesis , Chlorocebus aethiops , Cinnamates/chemical synthesis , Drug Design , Microbial Sensitivity Tests , Mycobacterium/genetics , Nucleic Acid Hybridization , Vero CellsABSTRACT
In an attempt to identify potential new agents active against tuberculosis, 20 novel phenylacrylamide derivatives incorporating cinnamic acids and guanylhydrazones were synthesized using microwave assisted synthesis. Activity of the synthesized compounds was evaluated using resazurin microtitre plate assay (REMA) against Mycobacterium tuberculosis H37Rv. Based on empirical structure-activity relationship data it was observed that both steric and electronic parameters play major role in the activity of this series of compounds. Compound 7s (2E)-N-((-2-(3,4-dimethoxybenzylidene) hydrazinyl) (imino) methyl)-3-(4-methoxyphenyl) acrylamide showed MIC of 6.49microM along with good safety profile of >50-fold in VERO cell line. Thus, this compound could act as a potential lead for further antitubercular studies.
