Production of effective and low cost dapsone-phytochemical hybrid candidate for use in multidrug therapy against Mycobacterium leprae

Student of Institute of Medical Sciences and Sum Hospital (IMS and Sum Hospital) Bhubaneswar, Shasank Sekhar Swain won the award for research work of Production of effective and low cost dapsone-phytochemical hybrid candidate for use in multidrug therapy against Mycobacterium leprae. They carried their project work under the guidance of Prof. Rabindra Nath Padhy, Prof. P. Sudhir Kumar.

Leprosy, the staggering infectious disease caused by the obligate intracellular Mycobacterium leprae continues to be the belligerent public health hazard for causation of high disability and eventual long-term morbidity, even treatment with ongoing multidrug therapy (MDT). From the vast ethnomedicinal records and ethnopharmacological investigations, phytochemicals are potent against infectious diseases; but, none of those has gone up to the pure-drug stage due to the lack of the desired drug-likeness values and the required pharmacokinetic properties. To overcome the drug-resistant problem, the improvement of the primary antileprosy sulfa drug, dapsone through chemical conjugation with a suitable phytochemical for reuse of dapsone in empiric antibacterial therapy is the primary goal. With various bioinformatics and chemoinformatics analysis, dapsone-phytochemical conjugates were synthesized adopting azo-dye coupling reaction, and structural interpretation was carried out by UV, FTIR, NMR, HPLC, LCMS, and SEM.

From the in vivo ‘mice-foot-pad-propagation’ study, the ‘dapsone-thymol’ hybrid product at the WHO recommended dose for dapsone, 0.01 % mg/kg reduced one-log bacilli-population in ‘dapsone-resistant’, and no bacilli were found in ‘dapsone-sensitive’ M. leprae infected mice foot-pad in three months of oral treatment. Additionally, from the in vitro host-toxicity study with cultured-human lymphocytes, it was confirmed that the dapsone-thymol conjugate was safe for oral administration up to 5,000 mg/L, since a minor number of dead cells were found under a fluorescent microscope. In conclusion, the newly synthesized ‘dapsone-thymol hybrid’ product could be used in a revised MDT in place of dapsone against M. leprae after successful validation in the clinical phase. Indeed, conjugation of a phytochemical with the obsolete drug could serve the new trend in current antibacterial drug development with resources and time saving through the ingenious combination of bioinformatics and medicinal chemistry tools.

The Hon’ble Vice President of India, Shri M. Venkaiah Naidu awarded the Gandhian Young Technological Innovation (GYTI) Award to Shasank Sekhar Swain, Institute of Medical Sciences and Sum Hospital (IMS and Sum Hospital) Bhubaneswar at the GYTI 2019 Awards function held at Vigyan Bhawan, New Delhi on July 06, 2019.

Leave a Reply

Your email address will not be published. Required fields are marked *