Research Groups

Molecular Medicine: Malaria Drug Discovery

Research Interests and Description

Group Leader: Dinkar Sahal, PhD

Group Members

Research Interests

Novel antimalarials through discovery from marine organisms, medicinal plants, fungal endophytes & Cyanobacteria, and by design via chemical synthesis, synergy, pharmacokinetics, in vivo efficacy.

Description of Research

Malaria continues to be ever more a serious problem. The simplistic versions of everything including drugs, vaccines and insecticides seem to have failed us. My laboratory is dedicated to working in both discovery and invention modes to identify a variety of pharmacophores against Malaria that will be safe, potent and affordable. In the discovery mode, following high throughput SYBR Green fluorescence based screening against P.falciparum in culture; we have identified several promising molecules from marine organisms, medicinal plants, Cyanobacteria and endophytic fungi. Successive activity guided RPHPLC fractionations have resulted in progressive purification to homogeneity with impressive enhancements in potency. Highly professional use of spectroscopic tools like NMR and mass spectral fragmentation patterns has started providing deep insights into the stereo chemical architectures of these promising compounds. Chemical synthesis by our collaborator Dr.Madhav Sharma at IICT, Hyderabad followed by chromatographic, spectroscopic and biological comparison has confirmed the molecular identity of Nature’s molecule with that obtained by chemical synthesis.

At this time, plans are afoot to engineer Nature’s molecules for enhanced drugability and affordability. It  is a matter of great joy that such a challenging task as consulting Nature to discover and modern chemistry to identify and synthesize Nature’s molecules in the laboratory is being accomplished through modestly funded but highly robust inter institutional collaborative programs supported by DBT, DST and the ICMR. In the invention mode we have designed and synthesized a library of chalcones, stilbenes, chalcones-stilbene hybrids , acridines, cryptolepins, pyrimidines and Quinolines that are potent against the Chloroquine resistant strains of malaria parasite and  not unduly toxic to mammalian cells. Deeply interesting is the finding that some of these synthetic molecules induce programmed cell death in the malaria parasite. Both the choice of the synthons and the methods of green chemistry used for their chemical synthesis are likely to ensure that when some of these molecules become drugs, they will be affordable for the teeming millions of the poor people that fall prey to Malaria for want of good and humane drugs. A programme for exploration of the endophytic fungi for their antimalarial pharmacophores from the medicinal plants of Cameroon is running on a war footing now. In the same vein, we have now embarked on a major project of identifying and isolating novel antimalarial pharmacophores from the non sporulating fungi associated with mangroves and sponges of Andaman Islands.

Recent Publications

Kaushik, N., Bagavan, A., Rahuman, A. A., Zahir, A. A., Kamaraj, C., Elango, G., Jayaseelan, C., Kirthi, A. V., Santhoshkumar, T., Marimuthu, S., Rajakumar, G., Tiwari, S. K., Sahal, D., 2015. Evaluation of antiplasmodial activity of medicinal plants from North Indian Buchpora and South Indian Eastern Ghats. Malaria Journal (In Press)

Singh, N., Kaushik, N.K., Mohanakrishnan, D., Tiwari, S. K., Sahal, D. 2015. Antiplasmodial Activity of Medicinal Plants from Chhotanagpur Plateau, Jharkhand, India. Journal of Ethnopharmacology. 165: 152–162. PubMed link

Suryanarayanan, T. S. , Gopalan, V., Sahal, D. and Sanyal, K. 2015. Establishing a national fungal genetic resource to enhance the bioeconomy. Current Science. 109: 1033-1037.

Sabareesh, V., Sahal, D. 2015. Explorations into conformationally distinct isomeric peptides of opposite directionalities by high resolution electrospray collision induced dissociation tandem mass spectrometry. International Journal of MassSpectrometry. 391: 31– 40.

Vijay Kumar and Dinkar Sahal. 2014. Genetic Engineering, Ullmann’s Encyclopedia of Industrial Chemistry

Veerabadhran M, Manivel N, Mohanakrishnan D, Sahal D, Muthuraman S. 2014. Antiplasmodial activity of extracts of twenty five    cyanobacterial species from coastal regions of Tamil Nadu. Pharm Biology. 52: 1291-301. PubMed link

International Workshop "Discovery of New Drugs Against Malaria"-  ISBN: 978-93-84869-16-8, 27th Jan-6th Feb, 2015. Composers:  Dinesh Mohankrishnan and Naveen Kaushik, Editor Dinkar Sahal.

ICGEB New Delhi

ICGEB Campus
Aruna Asaf Ali Marg
110 067 New Delhi
INDIA
Tel: +91-11-26741358/1007
Fax: +91-11-26742316
icgebicgeb.res.in

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