Antimalarial activities of colorotane sesquiterpenes isolated from Warburgia ugandensis: docking and medicinal analysis Joelle Nadine Mbieda, Laurent Eyia Endiga, Désiré Bikélé Mama University of Douala, Cameroon Background : The observation of therapeutic failures of multiple antimalarial protocols in sub-Saharan areas where acute malnutrition is highly prevalent is the main motivation for the choice of this topic. In view of the geographically isolated failures of artemisinin-based combination therapies, the problem of standardising protocols to assess the clinical relationship between malaria and malnutrition requires imperative reflection. To this end, the ethnobotanically validated inhibition of acute malaria (more so than chloroquine) by daily intake of Warburgia ugandensis tea by Ugandan and Kenyan populations needs to be exploited. Objective: Elect for each of the two problems the best life-saving molecule Methods: The geometric data B3PW91/6-31+G(d,p) is used as a starting point for each sesquiterpene colorotane. The evaluation of antimalarial activity was implemented by studying the ligand-analysis interaction of the plasmepsin X protein. The pharmacokinetic profile by applying Lipinski's, Oprea's and Verdonk's constraints was done. Results : The affinity of the ligand-plasmepsin X protein bond of our molecules are ranging from -7.13 to -4.81 kcal/mol. On the basis of this criterion, (5aS,7S,9aS,9bS)-1,5a,6,7,8,9,9a,9b-octahydro-1-hydroxy-7,9a-dimethyl- 6-methylenenaphtho[2,1-c]furan-3(5H)-one structure ( b ) can be elected as a structure with high affinity to the plasmepsin X protein. The examination of the potassium ion channel of the HERG can block the contribution to the electrical activity of the heart. Conclusion: All our molecules do not respect Verdonk’s rule except molecules (5aS,7S,9aS,9bR)- 1,5a,6,7,8,9,9a,9b-octahydro-9b-hydroxy-7,9a-dimethyl-6-methylenaphtho[2,1-c]furan-3(5H)-one a , (5aS,7S,9aS,9bS)-1,5a,6,7,8,9,9a,9b-octahydro-1-hydroxy-7, 9a-dimethyl-6-methylenaphtho[2,1-c]furan- 3(5H)-one b , (4R,5aS,7S,9aS)-4,5,5a,6,7,8,9,9a-octahydro-4-hydroxy-7,9a-dimethyl-6-methylenaphtho[2,1-c] furan-1(3H)-one d(R) and (4S, 5aS,7S,9aS)-4,5,5a,6,7,8,9,9a-octahydro-4-hydroxy-7,9a-dimethyl-6- methylenaphtho[2,1-c]furan-1(3H)-one d(S) ), more precisely the molecular weight MW, hydrogen bond donor HBD and hydrogen bond acceptor HBA except for the constraint logP(o/w). Hence no optimal gastrointestinal absorption by permeability to passive diffusion. a , b and d also encounter area polar surface standard but will not be able to cross skin membrane, will be able to cross gastrointestinal membrane, and will be able to carry the blood-brain membrane. They can be transported by human serum albumin but presage cardiac toxicity. References 1. Kuglerova M, et al ., Afr J Biotechnol 2011, 10:3628–3632 2. C.A. Lipinski; F. Lombardo; B.W. Dominy and P. J. Feeney, Experimental and computational approaches to estimating solubility and permeability in drug discovery and development media, in Adv Drug Del Rev, vol. 46 ( 1997), pp. 3-26, 3. Cabantchik, Z. I., Glickstein, H., Golenser, J., Loyevsky, M. and Tsafack, A. Iron chelators: mode of action as antimalarials. Acta Haematol. 95 ( 1996 ) 70–77. 4. Daniel F. Veber, Stephen R. Johnson, Hung-Yuan Cheng, Brian R. Smith, Keith W. Ward, and Kenneth D. Kopple, Molecular Properties That Influence the Oral Bioavailability of Drug Candidates J. Med. Chem 45 (2002) 2615-2623 5. Djossou F., Receveier M.C, Peichan E., Monlunie E. ; Clerc M., Longy-Boursier M., and Le Bras M. Stress oxydant et paludisme : A propos de Stress de 24 observations de paludisme à Plasmodium fafciparum. Bulletin de la. Société de Pathologie Exotique, 89 ( 1996 )17-23. 6. Du QS, Jiang ZQ, He WZ, Li DP. Amino acid principal component analysis (AAPCA) and its applications in protein structural class prediction. J Biomol Struct Dyn 23 ( 2006 ) 635–640.
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