IDENTIFICATION OF NATURAL LEAD MOLECULES OF CENTELLA ASIATICA AND AZADIRACHTA INDICA TARGETING CHOLERA TOXIN THROUGH STRUCTURE BASED DRUG DESIGN

2016-09-12T01-57-19Z
Source: Indo American Journal of Pharmaceutical Research
Kishore Sarma, Biswajyoti Borkakoty*, Pratap Parida, Sudipta Sankar Bora, P. K. Mohapatra, Dipanakar Biswas, Jagadish Mahanta.
Vibrio cholerae, the causative organism of cholera, infects the small intestine causing severe diarrhea that can lead to death if untreated. Cholera toxin (CT) is primarily responsible for exhibiting the cholera symptoms. Although in numerous study, anticholera activity of Centella asiatica and Azadirachta indica has been evaluated and proved, the active principles and their modes of action are still elusive. In order to unveil the active principles of Centella asiatica and Azadirachta indica as potential inhibitor of CT, a ligand library of the reported compounds from these two plants was prepared and was used for molecular docking against three putative drug targets of CT. Progressive knowledge of computer aided drug designing approach was employed to screen out novel lead candidates. Comparative molecular docking analysis inferred that kaempferol 7-O-glucoside, a flavonol glucoside of Centella asiatica had the highest binding affinity with two of the selected drug targets and third best binding affinity with the third drug target of CT. In silico ADME/Tox profiling showed least toxicity with low bioavailibility. This study suggested that kaempferol 7-O-glucoside has the highest binding affinity with the identified ligandable sites of active CT and may be considered as a candidate inhibitor of CT in the lumen of gastrointestinal tract. Further clinical trials of kaempferol 7-O-glucoside may lead to a candidate drug molecule to fight against cholera infection.


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