In:
Current Topics in Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 22, No. 19 ( 2022-07), p. 1611-1625
Abstract:
Leprosy (Hansen’s disease) is a neglected tropical disease affecting millions
of people globally. The combined formulations of dapsone, rifampicin and clofazimine (multidrug therapy, MDT) is only supportive in the early stage of detection, while “reemergence” is
a significant problem. Thus, there is still a need to develop newer antileprosy molecules either of natural or semi-synthetic origin. Objective: The review intends to present the latest developments in the disease prevalence, available
therapeutic interventions and the possibility of identifying new molecules from phytoextracts. Methods: Literature on the use of plant extracts and their active components to treat leprosy was
searched. Selected phytoconstituents were subjected to molecular docking study on both wild and mutant types of the Mycobacterium leprae. Since the M. leprae dihydropteroate synthase (DHPS) is
not available in the protein data bank (PDB), it was modelled by the homology model method and validated with the Ramachandran plot along with other bioinformatics approaches. Two mutations
were introduced at codons 53 (Thr to Ile) and 55 (Pro to Leu) for docking against twenty-five selected phytoconstituents reported from eight plants that recorded effective anti-leprosy activity. The
chemical structure of phytochemicals and the standard dapsone structure were retrieved from the PubChem database and prepared accordingly for docking study with the virtual-screening platform
of PyRx-AutoDock 4.1. Results: Based on the docking score (kcal/mol), most of the phytochemicals exhibited a higher
docking score than dapsone. Asiaticoside, an active saponin (-11.3, -11.2 and -11.2 kcal/mol), was proved to be the lead phytochemical against both wild and mutant types DHPS. Some other useful
phytoconstituents include echinocystic acid (-9.6, -9.5 and -9.5 kcal/mol), neobavaisoflavone (-9.2, -9.0 and -9.0 kcal/mol), boswellic acid (-8.90, -8.90 and -8.90 kcal/mol), asiatic acid (-8.9, -8.8 and
-8.9 kcal/mol), corylifol A (-8.8, 8.0, and -8.0), etc. Overall, the computational predictions support the previously reported active phytoextracts of Centella asiatica (L.) Urban, Albizia amara (Roxb.)
Boivin, Boswellia serrata Roxb. and Psoralea corylifolia L. to be effective against leprosy. Conclusion: A very small percentage of well-known plants have been evaluated scientifically for
antileprosy activity. Further in vivo experiments are essential to confirm anti-leprosy properties of such useful phytochemicals.
Type of Medium:
Online Resource
ISSN:
1568-0266
DOI:
10.2174/1568026621666210909162435
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2022
SSG:
15,3
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