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Home > Archives > Volume 20, No 8 (2022) > Article

DOI: 10.14704/nq.2022.20.8.NQ44525

Molecular Docking and Computational Analysis of Anti-Parasitic Drug Molecules Against Trypanosoma Cruzi – Causative Agent of Chagas Disease

Sweekriti Pathak, Navin Kumar, Saurabh Kumar Jha, Santosh Kumar Karn, Pallavi Singh

Abstract

Chagas disease, also known as Trypanosomiasis, is found mostly in Latin America by the infection of a parasite, Trypanosoma cruzi. It is considered to be vector born disease which is transmitted by an insect, Triatominae Bug. Other sources of transmission of disease are Blood transfusion, oral and Congenital transmission. According to WHO, it is the most ignored disease of tropical countries despite of the fact that more than 7 million people are found infected by it across the globe every year. Chagas Disease is listed in the group of twenty Neglected Tropical Diseases (NTDs). The study presented here is an attempt to explore potential inhibitors against Trypanosoma Cruzi by targeting the receptor protein, Cruzain which has a significant role in mechanism of infection and survival of this parasite inside the host cells. Cruzain, the primary cysteine protease of Trypanosoma cruzi, is critical for survival of the parasite in host cells, rendering it as an important target for development of inhibitors. Cruzain has been related with parasite metabolism and identified as both an important candidate for vaccine development and for trypanocidal drug design. Recent observations suggest that sulfonamides and hydrazide derivatives possess antiparasitic activity and holds promise as anti trypanosomal chemotherapeutic agents suggesting their use as inhibitors to the protease. In this study, around five hundred sulfonamides and hydrazide derivates and their similar conformers were screened using virtual screening and ultimately 50 conformers werer chosen on the basis of the structural specificity to the enzyme towards its substrate and inhibitors. Using an exhaustive virtual-screening, docking and ADMET study in our work, we have identified 4-tert-butyl-N-[2-[4-(furan-2- carbonyl)piperazin-1-yl]-2- oxoethyl]benzene sulfonamide as the most potential efficient lead molecule against cruzain protein to treat chagas disease. Binding affinity of this molecule was -7.2 Kcal/mol which shows highly stable complex and it has exhibited drug likeness score of 0.78 and TPSA value of 86 with high potential for absorption in GI tract with no associated toxicity, mutagenicity, reproductive toxicity risk and has shown a great blood brain penetration coefficient.

Keywords

Insilico analysis, Chagas disease, Trypanosoma Cruzi, Cruzain Protein, Benzene sulfonamide, Drug designing, Virtual Screening, Molecular Docking

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