Design, synthesis and antimycobacterial activity of new molecules

 

 

The current understanding of cellular biochemistry of mycobacteria and, therefore, on potential new cellular targets in TB treatment, prompted the research in the development of new compounds with promising anti-mycobacterial activity.

One of these targets, which has been recently identified, relates to the biosynthesis of menaquinone (vitamin K2) whose biosynthesis is absent in the human being, so potential target molecules for selective antitubercular; menaquinone is involved in the electron transport chain in many pathogens, including Mycobacterium tuberculosis. Among the various enzymes involved in this pathway, the MenB is the most interesting; it catalyzes the intramolecular Claisen condensation reaction leading to the formation of DHNA-CoA from o-succinylbenzoate-CoA (OSB-CoA). Inhibition of this enzyme leads to the block of the vitamin K2 biosynthesis, essential for the mycobacteria viability. Our research group deals with the synthesis of new molecules as inhibitors of MenB, with particular attention to the benzoxazinone-type scaffold.

 

Main publications:

1. D. Zampieri, M.G. Mamolo, L. Vio, E. Banfi, G. Scialino, M. Fermeglia, M. Ferrone, S. Pricl, “Synthesis, antifungal and antimycobacterial activities of new bis-imidazole derivatives, and prediction of their binding to P45014DM by molecular docking and MM/PBSA method.” Bioorg. Med. Chem., 15 (2007), 7444-7458.

2. D. Zampieri, M.G. Mamolo, E. Laurini, G. Scialino, E. Banfi, L. Vio, M. Fermeglia, M. Ferrone, S. Pricl, “Antifungal and antimycobacterial activity of 1-(3,5-diaryl-4,5-dihydro-1H-pyrazol-4-yl)-1H-imidazole derivatives.” Bioorg. Med. Chem., 16 (2008), 4516-4522.

3. D. Zampieri, M.G. Mamolo, E. Laurini, M. Fermeglia, P. Posocco, S. Pricl, E. Banfi, G. Scialino, L. Vio, “Antimycobacterial activity of new 3,5-disubstituted-1,3,4-oxadiazol-2(3H)-one derivatives. Molecular modeling investigation.” Bioorg. Med. Chem., 17 (2009), 4693-4707.

4. D. Zampieri, M.G. Mamolo, E. Laurini, G. Scialino, E. Banfi, L. Vio, “2-Aryl-3-(1H-azol-1-yl)-1H-indole derivatives: a new class of antimycobacterial compounds. Conventional heating in comparison with MW-assisted synthesis.” Arch. Pharm Chem. Life Sc., 342 (2009) 716-722.

Research Group

Mamolo and Zampieri Group
Last update: 12-13-2019 - 19:50