Harale, Bhaiyyasaheb and Kidwai, Saqib and Ojha, Divya and Singh, Manisha and Chouhan, Dwarika Kumar and Singh, Ramandeep and Khedkar, Vijay and Rode, Ambadas B. (2021) Synthesis and evaluation of antimycobacterial activity of riboflavin derivatives. Bioorganic & Medicinal Chemistry Letters, 48. p. 128236. ISSN 0960894X

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Abstract

The riboflavin biosynthetic pathway is a promising target for the development of novel antimycobacterial drugs given the lack of riboflavin transporter in M. tuberculosis. Herein, a series of riboflavin derivatives was designed, synthesized and screened for their antimycobacterial and antibacterial activity. The compounds 1a, 1b, 2a, 3a and 5a displayed noticeable antitubercular activity against M. tuberculosis with minimum inhibitory concentration (MIC99) in the range of 6.25 to 25 μM. The lead compound 5a had a selectivity index of 10.7 in the present study. The compounds 2a, 2b, 2c, 4c and 4d showed relatively low to moderate antibacterial activity (MIC = 100–200 μM) against gram-positive strains. Notably, the compounds do not show any inhibition against gram-negative strains even at 200 μM concentration. Further, molecular docking and binding experiments with representative flavin mononucleotide (FMN) riboswitch suggested that the riboflavin analogs exhibited antimycobacterial activity plausibly through FMN riboswitch-mediated repression of riboflavin biosynthesis. In addition to FMN riboswitch, flavoproteins involved in the flavin biosynthesis could also be target of riboflavin derivatives. In conclusion, the potency and low toxicity of riboflavin analogs particularly 5a (MIC99 = 6.25) make it a lead compound for the synthesis of new analogs for antimycobacterial therapy.

Item Type:	Article
Subjects:	Biomedical Science
Depositing User:	RCB Library
Date Deposited:	02 Aug 2021 07:57
Last Modified:	02 Aug 2021 07:57
URI:	http://rcb.sciencecentral.in/id/eprint/612

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