The use of drug substances derived from plants, fungi, bacteria, and marine organisms are ‘‘Mother Nature Gift’’ for diseases of mankind. Many of these are discovered serendipitously and have a long tradition in medicine. Till date, the use of natural products, their semisynthetic and synthetic derivatives have been mostly confined to their ethnic use. But it has been well known that each substance has a wide spectrum of biological activities as evident from some new uses of many old drugs. PASS (Prediction of Activity Spectra for Substances) has been employed as a strong potential tool to predict the biological activity spectrum of synthetic substances for the discovery of new drugs. But the potential of PASS to predict the biological activity spectra of natural products is still underestimated. The present study was therefore undertaken to investigate and correlate the biological activity spectrum of the main phytoconstituent of some selected Indian medicinal plants with their reported biological activities in order to evaluate the applicability of PASS. Further, the unexplored but PASS-predicted activities having good activity score (Pa>0.7) for particular structure were listed as hidden potential of the plant.
Med. Chem. Res., 2011, 20 (9), 1509-1514.

Natural products found a wide use in folk medicine. Presently, when routine development of new drugs faced a considerable challenge, they become an inspiration and valuable source in drugs discovery. Rather complex and diverse chemical structures of natural compounds provide a basis for modulation of different biological targets. Natural compounds exhibit a multitargeted action that may lead to additive/synergistic or antagonistic effects. Rational design of more safe and potent pharmaceuticals requires an estimation of probable multiple actions of natural products. Our software PASS can perform such estimation. It predicts with reasonable accuracy over 3500 pharmacotherapeutic effects, mechanisms of action, interaction with the metabolic system, and specific toxicity for drug-like molecules on the basis of their structural formulae. We analyzed PASS predictions utilizing PharmaExpert, which performs selection of compounds with multiple mechanisms of action, analysis of activity-activity relationships and drug-drug interactions. The paper describes an application of PASS and PharmaExpert to the evaluation of biological activity of natural compounds including marine sponge alkaloids, triterpenoids of lupane group, and their derivatives. Proposed computer-aided methods can generate combinatorial libraries of macrolides. They help to select the most promising pharmaceutical leads with the required properties. Case study, based on the analysis of biological activity spectra predicted for St John’s Wort constituents, clearly demonstrates capabilities of computational methods in the evaluation of multitargeted actions, additive/synergistic and/or antagonistic effects of natural products.
Current Pharmaceutical Design, 2010, 16 (15), 1703-1717.