Pyrrolyl thiadiazoles as Mycobacterium tuberculosis inhibitors and their in silico analyses

Shrinivas Joshi, Uttam More, Shailesh Sorathiya, Deepshikha Koli, Tejraj Aminabhavi
2015 Research and Reports in Medicinal Chemistry  
A novel series of pyrrolyl thiadiazoles was synthesized and tested for antimycobacterial activity against the Mycobacterium tuberculosis H 37 Rv strain, using the microplate Alamar blue assay method. Molecular docking and in vitro minimum inhibitory concentration assays revealed that these molecules can be primarily screened for ENR inhibition, using the score values and H-bond interactions with amino acid residues Tyr158, Met98, and cofactor NAD + , which are the key interactions. For most of
more » ... tions. For most of the molecules, hydrophobic interaction is the key factor affecting their antitubercular activity. The activity of -OCH 3 , -NO 2 , -F, pyridine, and sulfonamide substituted derivatives was better than that of -CH 3 , -NH 2 , -Cl, and -Br substituted derivatives, as per experimental and docking studies. Molecular modeling studies are in agreement with their biological evaluations. submit your manuscript | www.dovepress.com Dovepress Dovepress 2 Joshi et al Figure 1 Reported molecules; pyrrole connected to heterocycles (oxadiazole, triazole, pyrazolo[3,4-b]quinolin-1-yl, naphtha[2,1-b]furan-2-yl) through phenyl bridge. Abbreviations: CheMBl, chemical database of bioactive molecules with drug-like properties; MiC, minimum inhibitory concentration. Research and Reports in Medicinal Chemistry downloaded from https: //www.dovepress.com/ by 207.241.231.83 on 24-Jul-2018 For personal use only. Powered by TCPDF (www.tcpdf.org)
doi:10.2147/rrmc.s80395 fatcat:iob5gkaj7zg2vaw3v57ymvwp54