Screening, identification and evaluation of some novel target specific therapeutic compounds against Trypanosoma evans
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Date
2022-06
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Lala lajpat rai university Hisar
Abstract
The Trypanosoma evansi is the most pathogenic animal trypanosome, which leads to annual
economic loss of US $ 671.1 million in India. Limited drug availability, high toxicity, severe side
effects and emerging drug resistance necessitate the investigation of novel and safer chemotherapeutic
agent. Therefore, in the present study, a total of 36 drug molecules were evaluated for their anti trypanosomal activity against T. evansi and cytotoxicity against mammalian cells. Drugs were divided
into 4 categories, viz. novel target specific drugs (11), re-purposing based drugs (7), drugs effective on
other kinetoplastids (6) and antibiotics (12) and they were investigated for their mode of action by
studying the mRNA expression of 13 drug target genes using qPCR. Drugs with high anti trypanosomal activity and low cytotoxicity were evaluated for therapeutic efficacy in mice model. In
the novel target specific drugs, etoposide and IC-261 increased the longevity of T. evansi infected mice
by 48 h in comparison to control mice. Among the drugs effective on other kinetoplastids,
amphotericin B raised the survival period of mice by 120 h. Nifurtimox and buparvaquone checked the
level of parasitaemia on regular injection. However, imidocarb raised the survival period of mice by 20
days without any significant organotoxicity. Data generated showed that qPCR profile of highly
efficient anti-trypanosomal drug was similar to standard drugs and imidocarb can be suggested as an
alternate therapeutic compound for treatment of Surra infection. The data generated will be of immense
use in future drug development strategies for curtailment of Surra in animals.