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Molecular Docking Studies and In-silico Computational Analysis of Analogs of Anti-malarial Drugs

Santosh Kumar Behera1, Amrita Panda1, Mahendra Rana2 and Satpal Singh Bisht1

1. Department of Zoology, Kumaon University, Nainital, Uttarakhan, India

2. Department of Pharmaceutical Sciences, Bhimtal, Kumaun University, Nainital, Uttarakhand, India


Abstract: Malaria is a major global threat resulting more than 2 million deaths each year caused by protozoan parasites namely, Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi, P. falciparum is the causative agent of severe malaria and the major cause of malaria-related fatality. Widespread drug resistance against currently available anti-malarial warrants the identification of novel drug targets and development of new drugs that should be economical, fast effective and safer to all age groups. Proguanil is a prophylactic anti-malarial drug, a biguanide derivative which stops the reproduction of the malaria parasite, P. falciparum and P. vivax, once it is entered in the red blood cells by inhibiting the enzyme, Pf-dihydrofolatereductase (Pf-DHFR) that halts the paracitic lifecycle. The mutations in the receptor proteins tend to resistance towards proguanil due to weak binding affinity which could be overcome by development of analogs of proguanil. In the present study an attempt was taken to find out the analogs of proguanil through an in-silico approach which could be a potential anti-malarial inhibitor that acts against malarial target Pf(TS-DHFR) (Thymidylate Synthase Dihydrofolate Reductase) that play a key role in parasitic life cycle. The molecular docking analysis reported of PfTS-DHFR-Proguanil was -7.41 Kcal/mol, whereas the docking studies of PfTS-DHFR with ZINC00001127 and ZINC16343331 (Analogs of proguanil) were -9.14 and -8.7 Kcal/mol. This states that the analogs of proguanil may be of therapeutic importance for malarial patients which has an effective role in clearing parasites from the human biological system.

Key words: Analogs, drug resistance, malaria, proguanil, PfTS-DHFR.
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