• Savita Ajit Patil
• Amol Thete
• Sudarshan Shelake
• Dwarkanath Bhagat

Malaria is a dreadful disease caused by the parasite Plasmodium and is transmitted to humans by mosquitoes. Malaria remains an important public health problem, especially in endemic regions of India. Globally, malaria remains a leading infectious disease, and especially so in Sub-Saharan Africa and South East Asia. Global efforts are underway to eliminate malaria and to use a multi-pronged strategy where drugs play a crucial part. The most effective present day line of treatment option is based on the artemisinin-based drugs. The malarial parasites are developing resistance to the artemisinin class of drugs; it is likely that one day these drugs will be ineffective. Therefore, there is an urgent need to develop new classes of anti-malaria drugs with novel modes of action.Cladosporin (also known as asperentin), 3,4-dihydro-6,8-dihydroxy3-(6-methyl tetrahydropyran-2-ylmethyl) isocoumarin, is an important secondary metabolite isolated from Cladosporium cladosporioides in 1971. It is the major compound of C. cladosporioides, but a minor metabolite of other fungal sources including Aspergillus flavus. In Present study we have assessed the fungal metabolite-inspired molecules (Cladosporin stereoisomers) as potential lead antimalarials. Novel synthetic routes were developed in the laboratory to access this natural product. In addition, the team has synthesized all the possible stereoisomers of Cladosporin using novel synthetic organic chemistry protocols. After the successful synthesis of all eight compounds (called Cladologs), the teams tested it against malaria parasites to address their potency. Enzyme and structure-based studies were done to address mechanistic details of the drug interactions. The important cladologs were co-crystallized with the target enzyme lysyl-tRNA synthetase of malaria parasite in order to provide atomic details. The bases for wide differences in antimalarial potency between various sterioisomeric forms of cladosporin using an elegant chemistry, strong biochemisty and modern structure-based methods. Three categories of molecules as potent, moderately potent and non-potent were identified based on target binding and parasite killing. The demonstrations validated two most potent stereoisomers of cladosporin so this information will allow their development for drug-like properties. The significance of chirality in modern drug discovery has also been highlighted through these efforts.

"Potential leads for development of new antimalarial drugs", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.6, Issue 6, page no.512-525, June 2019, Available :http://www.jetir.org/papers/JETIR1908684.pdf

"Potential leads for development of new antimalarial drugs", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.6, Issue 6, page no. pp512-525, June 2019, Available at : http://www.jetir.org/papers/JETIR1908684.pdf