Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety

Chemistry Central Journal
Mostafa M GhorabMahmoud M Elaasser

Abstract

A series of novel N-(2, 6-dimethoxypyrimidin-4-yl)-4-(3-(aryl)thioureido) benzenesulfonamides 3a-t was synthesized by the addition of N-(2,6-dimethoxypyrimidin-4-yl)-4-isothiocyanatobenzenesulfonamide 2 to the appropriate aromatic amine. The structures of the synthesized compounds were inspired from the second line antituberculosis pro-drugs. Most of the new compounds were screened for their activity against Mycobacterium tuberculosis. The results of the antimycobacterial assay showed that compound 3i exerted the highest activity (MIC = 3.13 µg/mL), followed by compound 3s (MIC = 6.25 µg/mL). The structure-activity relationship (SAR) analysis revealed that the introduction of the benzo[1,3]dioxol moiety in 3i and the 4-morpholinyl-4-phenyl moiety in 3s has proven to give the most potent compounds in this study. Docking of the promising compounds inside the active site of M. tuberculosis enoyl reductase InhA was performed in order to emphasize the results. The compounds showed a similar orientation to that of GSK 625 inside the active site of 5JFO and bind to Met 98 in a way similar to that of the co-crystallized ligand.

References

Apr 14, 1999·Molecular Microbiology·H ChristensenM R Barer
Jun 27, 2001·Bioorganic & Medicinal Chemistry Letters·I KüçükgüzelM Kiraz
May 3, 2005·Bioorganic & Medicinal Chemistry Letters·Rosanna MaccariMaria Gabriella Vigorita
Nov 24, 2005·Bioorganic & Medicinal Chemistry Letters·Dharmarajan SriramKasinathan Madhu
Aug 1, 2006·Bioorganic & Medicinal Chemistry Letters·Veemal BhowruthGurdyal S Besra
Jan 24, 2007·European Journal of Medicinal Chemistry·Mahendra ShiradkarRachit Shah
Nov 24, 2007·Annual Review of Microbiology·Catherine Vilchèze, William R Jacobs
Apr 15, 2008·Drug Discovery Today·Giulio VistoliBernard Testa
Feb 5, 2009·Expert Opinion on Pharmacotherapy·Carole D MitnickCharles A Peloquin
Jan 9, 2010·Bioorganic & Medicinal Chemistry Letters·Sumesh EswaranImran H Chowdhury
May 1, 2013·Nature Reviews. Drug Discovery·Alimuddin ZumlaStewart T Cole
Oct 10, 2013·Bioorganic & Medicinal Chemistry·Marieli O RodriguesMarcelo G Montes D'Oca
Jul 6, 2015·European Journal of Medicinal Chemistry·Aurélien CholletMichel Baltas
Apr 5, 2016·Biological & Pharmaceutical Bulletin·Esra Tatarİlkay Küçükgüzel
Jul 20, 2016·EBioMedicine·María Martínez-HoyosAlfonso Mendoza-Losana

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Citations

Dec 7, 2018·Current Medicinal Chemistry·Maurício Boff de ÁvilaWalter Filgueira de Azevedo
Mar 29, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Carmen LimbanDiana Camelia Nuta
Apr 20, 2021·ACS Omega·Vallabhaneni S MurthyVijayaparthasarathi Vijayakumar

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