INFECTIOUS DISEASES / Parasitic Diseases
Discovery of potent, safe and affordable novel drugs against malaria,from nature, medicinal plants, Agbo-iba, Endophytic Fungi, Andaman and Nicobar Islands, Endophytic Actinobacteria, High throughput screening, antiplasmodial activity guided chromatographic purification, Synthetic drug like molecules, Trioxanes, Quinolines, Cryptolepines, Chalcones, GAP-50 and Pyridoxal Synthase as drug targets, in silico docking, Biacore, Resistance & Selectivity Indices, In vivo toxicity, antimalarial activity.
Description of Research
Nature is well known to make exquisite molecules with drug like properties. In this context, we are exploring the antimalarial potential of (a) a hepta-herbal combo designated as Agbo-iba from the Traditional medicine system of Nigeria, (b) non-sporulating endophytic fungi collected from Andaman Islands, (c) endophytic actinobacteria obtained from forest ecosystems of NortheastIndia which is a part of Indo-Burma mega-biodiversity hotspot (d) marine organisms from the coasts of India (e) medicinal plants from Himalayas and from the forests of South India. We rely on Giemsa microscopy and high throughput SYBR Green assay in 96 well micro titer plates to culture P.falciparum in human red blood cells and examine the growth inhibitory potencies of test substances. We first perform molecular properties based solvent fractionation to identify fractions with the highest potency and lowest toxicity. We then subject the potent fractions to Normal Phase-Reverse Phase two dimensional chromatography to isolate highly potent antiplasmodial molecules. At every step of purification, we keep an account of yield, purity, antiplasmodial IC50, together with Resistance and Selectivity indices. We intend to go for Academia Industry partnership for the development of four marine organisms derived potent antiplasmodial molecules into novel drugs against malaria. Alongside nature derived molecules, we also study the antimalarial potential of chemically synthesized molecules of diverse classes e.g. Quinolines, Trioxanes, Cryptolepines, Chalcones (C), Stilbenes (S), C-S hybrids, Azoles, Pyrimidines, Indoles, Aplysynopsins, Peptides and nanoparticles of gold, silver and curcumin. We use optical and fluorescence based microscopic methods to evaluate stage specificity and kinetics of drug action as also cytostatic vs cytocidal actions. We study antiplasmodial molecules in combinations to examine synergy. In addition to whole organism based screening, we also perform target based screening where our drug targets are hemozoin synthesis, recombinantly expressed malaria parasite proteins that are involved in (a) the invasion machinery and (b) the Pyridoxine biosynthetic pathway.
Sharma, U.K., Mohanakrishnan, D., Sharma, N., Equbal, D., Sahal, D., Sinha, A.K. 2018. Facile synthesis of vanillin-based novel bischalcones identifies one that induces apoptosis and displays synergy with Artemisinin in killing chloroquine resistant Plasmodium falciparum. Eur J Med Chem 155, 623-638 PubMed link
Ateba, J.E.T., Toghueo, R.M.K., Awantu, A.F., Mba’ning, B.M., Gohlke, S., Sahal, D., Rodrigues-Filho, E., Tsamo, E., Boyom, F.F., Sewald, N., Lenta, B.N. 2018. Antiplasmodial Properties and Cytotoxicity of Endophytic Fungi from Symphonia globulifera(Clusiaceae). J Fungi 12, 4 PubMed link
Toghueo, R.M.K., Sahal, D., Zabalgogeazcoa, Í., Baker, B., Boyom, F.F. 2018. Conditioned media and organic elicitors underpin the production of potent antiplasmodial metabolites by endophytic fungi from Cameroonian medicinal plants. Parasitol Res 117, 2473-2485 PubMed link
Mbouna, C.D.J., Kouipou, R.M.T., Keumoe, R., Tchokouaha, L.R.Y., Fokou, P.V.T., Tali, B.M.T., Sahal, D., Boyom, F.F. 2018. Potent antiplasmodial extracts and fractions from Terminalia mantaly and Terminalia superba. Malar J 17 PubMed link
Amlabu, W.E., Nock, I.H., Kaushik, N.K., Mohanakrishnan, D., Tiwary, J., Audu, P.A., Abubakar, M.S., Sahal, D. 2018. Exploration of antiplasmodial activity in Acalypha wilkesiana Müller Argoviensis, 1866 (family: Euphorbiaceae) and its GC-MS fingerprint. Parasitol Res 117, 1473-1484 PubMed link
Okokon, J.E., Antia, B.S., Mohanakrishnan, D., Sahal, D. 2017. Antimalarial and antiplasmodial activity of husk extract and fractions of Zea mays. Pharm Biol 55, 1394-1400 PubMed link