Identification of potential inhibitors of Leishmania donovani Sterol 24-C- methyltransferase: in silico and in vitro studies

ABSTRACT

Leishmania donovani causes the neglected tropical disease visceral leishmaniasis. There is currently no vaccine available to combat the disease. Therefore, chemotherapy is the only treatment option available. However, the available drugs have various adverse effects on the host. As a result, new drugs are needed to treat the disease; natural compounds can be used as an alternative to traditional drugs. This study examined apigenin, diosmin, and naringin as prospective inhibitors against the Leishmania donovani Sterol 24-C- methyltransferase enzyme (LdSMT). All three compounds have a high affinity for the LdSMT and remain stable for 100 ns during the molecular dynamics simulation. In the cell viability assays, these compounds showed excellent IC50 values, with apigenin having the best IC50 value of 16.11 µM against Leishmania donovani promastigote. The findings of this study showed that all three flavonoids could be used as a safe alternative to conventional anti-leishmanial drugs.

KEYWORDS:

• Leishmaniasis
• flavonoids
• simulation
• free energy
• MTT assays

Acknowledgements

Author contribution statements: SS, RS, PS, TKB, AP and DK experimented. SS, RS, TKB, AP and DK wrote the manuscript. SS, RS, TKB, AP and DK contributed to the analysis of the results. DK supervised the project and conceived the original idea.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The lab is supported by the Department of Biotechnology (India) (order no: BT/PR16224/NER/95/176/2015 & BT/PR24504/ NER/95/746/2017) to Dr Diwakar Kumar. Satabdi Saha and Parishmita Sarma recognises the financial support from the INSPIRE Fellowship (IF180806 & IF210083, respectively).