Screening of small molecules against malaria parasite | Shiv Nadar University
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Screening of small molecules against malaria parasite

Vijeta Sharma, Ph.D. Scholar, Department of Life Sciences, SoNS;  Faculty Advisor – Dr. Shailja Singh; Co-Advisor – Dr.Subhabrata Sen

Malaria still remains one of the world’s most devastating diseases and is a major global health challenge. Millions of people are at the risk of malaria globally, mostly affecting the Sub-Saharan Africa region. It is caused by an apicomplexan parasite of genus Plasmodium. Emergence and spread of the resistance to the current chemotherapy and non-availability of vaccine have made the development of the novel antimalarial drugs inevitable. Our research focuses on screening of library of chemically bioactive compounds for the identification and evaluation of the novel class of antimalarial drugs by Phenotypic screening and Target based screening approaches of drug discovery.

Malaria is a life threatening infectious disease being one of the major global health challenges. 212 million cases of malaria occurred globally according to the WHO Malaria Report 2016. Human malaria is caused by four main sps. of apicomplexan parasite of genus Plasmodium viz. Plasmodium falciparum, P. malariae, P. vivax and P. ovale. P. falciparum is responsible for the majority of the deaths and its infection predominates Africa. Artemisinin based combination therapy (ACT) is the gold standard for malaria treatment as the first line of treatment recommended by WHO which has been thwarted by the emergence of the resistance to ACTs in many malaria affected countries. Hence, there is an immediate need for the development of a new class of antimalarial drugs for the treatment of malaria.We explore the different classes of chemically bioactive compounds for their antimalarial activity. Our research focuses on the antimalarial drug discovery. Broadly phenotypic screening and target based drug discovery remained to be fascinating and advantageous in the identification antimalarial compounds. We screen library of novel chemical scaffolds which are synthesised by unique strategies such as diversity oriented synthesis (DOS), green chemistry, medicinal chemistry etc.

Phenotypic screening requires the identification of the anti-parasitic compounds by the use of whole cell based assays in which effect of the compounds on the growth and proliferation of the different blood stage parasites, drug sensitive and drug resistant strains, is observed upon treatment with the compounds. The lead screens obtained from screening the libraries of compounds showing best antimalarial activity are assessed for the lead optimisation, target validation and identification. Another approach, which we use is the target based screening for the identification of the lead compounds. The targets could be proteins having crucial cellular and molecular functions which show druggability and inhibition of which poses antiparasitic activity.

A DOS-mediated exploration of substituted bicyclic lactams with novel structural motifs and natural product based DOS library of hybrid systems generated via “privileged scaffolds” culminate in identifying a potential lead molecule against malaria parasite. We have screened 1, 3 benzoxazine derivatives of phytophenol synthesised by green chemistry showing promising antimalarial activity by disrupting sodium homeostasis. Concurrently, we screen the compounds against the potential targets having roles in the crucial mechanisms of the parasite like egress and redox homeostasis.