Research has shown that drugs or therapeutic agents which are directed at a particular target often undergo a reduction in efficacy, undesired safety profiles, compensatory and neutralizing effects, anti-target and counter target activities and also resistance against the drug. Proper utilization of multiple targets can lead to a perfect blend between the efficacy and safety when compared against single-targeted drug design. The authors have utilized this concept in case of the antifungal drugs which generally act against one of the targets amongst chitinase, chitin synthase, 1, 3 beta glucan synthase and lanosterol 14 α-demethylase. Henceforth, the present study is an attempt to screen the known drugs for their multi-targeting nature, and to compare natural product based drugs with semi-synthetic and synthetic drugs in-silico.
In the present study, eleven (7 synthetic and 4 natural) drugs namely Allosamidine, Methylxanthine, Acetozolamide, Nikkomycin Z, Polyoxin L, Caspofungin, Fluconazole, Argifin, Obovatol, Papulacandin and Ro-091470 have been chosen to study their effect against different targets.
This exciting and unique in-silico study provides insight that some drugs can function equally good against all targets, while some have a better efficiency against a different target than the known one. All four studied natural product based drugs are found to be good at multi-targeting. All the drugs that were shown to have a good multi-targeting efficiency bind at the same region where the known drugs against that target bind. Furthermore, lanosterol 14 α-demethylase is found to be the best target amongst all the aforesaid fungal targets.
Multi-targeting; In-silico; FireDock; Binding Energy; Drug designing