Rosmarinic acid and its derivative’s duel as antitubercular agents: insights from computational prediction to functional response in vitro

Abstract

Tuberculosis is one of the most dreadful infectious diseases, afflicting global populations with anguish. With the emergence of multi-drug resistant strains of mycobacteria, the imperative for new anti-tuberculosis drugs has grown exponentially. Thus, the current study delves into evaluating the impact of Perovskia abrotanoides and its active metabolites-namely, rosmarinic acid and its derivatives-against strains of Mycobacterium tuberculosis (Mtb). Through the use of the CRI assay, the antimycobacterial potential of the high-altitude medicinal plant P. abrotanoides was gauged, while docking and molecular dynamics simulations unveiled plausible targets. Of these, the peak antimycobacterial effectiveness was observed in the P. abrotanoides ethyl acetate extract with 125 µg/mL as minimum inhibitory concentration against various strains of M. tuberculosis, encompassing H37Rv and strains resistant to multiple drugs. Following bioassay-guided fractionation and isolation, rosmarinic acid and rosmarinic acid methyl ester emerged as potent molecules against H37Rv and multidrug-resistant M. tuberculosis strains; minimum inhibitory concentration ranging from 15 to 32 µg/mL. Additionally, out of 22 targets explored, Mtb lipoamide dehydrogenase (PDB: 3II4) and Rv2623 (PDB: 3CIS) were forecasted as potential Mtb targets for rosmarinic acid and rosmarinic acid methyl ester, respectively, a supposition further affirmed by molecular simulations (100 ns). The stability of both complexes throughout the simulation was measured by protein backbone root-mean-square deviation, substantiating their roles as respective targets for antimycobacterial activities.

Communicated by Ramaswamy H. Sarma

Keywords:

• Perovskia abrotanoides
• rosmarinic acid
• tuberculosis
• molecular docking
• molecular dynamics

Acknowledgment

The authors thank Sarman Joshi of AIIMS, New Delhi, S. Kitchlu of IIIM (CSIR), Jammu, and Dr. Sabari Ghosal of Amity University Noida, Uttar Pradesh for providing facilities to carry out this work.

Author contribution

NS, PK: Data curation, Draft, Edit, Review, RR: Data curation, YND, KKR: Draft, Edit, Review, Supervise

Disclosure statement

All the authors of this manuscript declare that they do not have any conflict of interest by any financial and non-financial means.

Additional information

Funding

Yadu Nandan Dey and Kuldeep K. Roy also wish to thank Science and Engineering Research Board, Department of Science and Technology for providing necessary facilities for the projects through Grant Number SRG/2021/001631 and SRG/2021/001734, respectively.