University of Pune is working on natural products drug discovery to accelerate the clinical candidate development. The University has now adopted the reverse pharmacology approach to develop efficient platforms for herbal formulations.

Pharmaceutical industry is now making a significant shift from single to multi targeted drugs. Strategic options based on natural product drug discovery and traditional medicines are re-emerging as an attractive discovery engine. In fact, relevant case studies from India and other countries indicate that the natural product drug discovery and development has helped to reduce time and economize investments with better safety. “We are also engaged in looking at many of these,” said Prof. Bhushan Patwardhan, vice chancellor, Symbiosis International University, Pune.

Saturation of the blockbuster drug pipeline is a major challenge for  pharma industry as the discovery process is extremely expensive, riskier and critically inefficient. This is where many active compounds from traditional medicine sources could serve as good scaffolds for rational drug design, he added.

Old molecules are finding new applications through traditional knowledge and clinical observations. For instance, forskolin an alkaloid isolated by Hoechst and coleonol by Central Drug research Institute (CDRI), CSIR, Lucknow from Coleus forskohlii  and phyto-chemicals from Stephania glabra, which were shelved for a considerable time are now being rediscovered as adenylate cylase and nitric oxide activators, which may help in obesity and atherosclerosis. Antimicrobial berberine alkaloids are now being rediscovered as novel cholesterol-lowering drugs working through different mechanism than statins. Potent anti microbial antirheumatic and cyclooxygenase inhibitory activities of phenolics, catechols and flavonoids  are from an important Ayurvedic plant, said Prof. Patwardhan.

Combinatorial chemistry developed using natural product scaffolds are being used to create screening libraries that closely resemble drug-like compounds. Most of these compounds are part of routinely used traditional medicines and hence their tolerance and safety are better known than any other chemical entities that are new for human use, pointed out Prof. Patwardhan.

Promising lead molecules have come out of Ayurvedic experiential base including Rauwolfia alkaloids for hypertension, Psoralens in Vitiligo, Holarrhena alkaloids in Amoebiasis, Guggulsterons as hypolipidemic agents, Mucuna pruriens for Parkinson’s disease, piperidines as bioavailability enhancers, baccosides in mental retention, picrosides in hepatic protection, phyllanthins as antivirals, curcumines in inflammation, withanolides, and other steroidal lactones and glycosides as immunomodulators, he said.

In a report on natural products drug discovery: Accelerating the clinical candidate development using reverse pharmacology approaches published in the Indian Journal of Experimental Biology, Prof. Patwardhan and Dr  Ashok D B Vaidya , research director, Kasturba Health Society Medical Research Center, Mumbai said that the pharmaceutical industry needs successes like artemisinin and reserpine. Many leads like curcumins and withanoloides are available but such R&D cannot ensue in isolation. Best of public and private sector partners comprising academia and industry should come together to reap benefits from research based on traditional knowledge.