Evaluation of antiparasitic activity and immunomodulatory potential of in vitro screened novel chalcones derivatives in Plasmodium berghei NK-65 (Chloroquine resistant) infected experimental mice

[Speaker] Shweta Sinha:1
[Co-author] Bikash Medhi:1, B D Radortra:1, Daniela I Batovska:2, Rakesh Sehgal:1
1:POST GRADUATE INSTITUTE OF MEDICAL EDUCATION AND RESEARCH, India, 2:Institute of Organic Chemistry with Centre of Phyto Chemistry Bulgarian Academy of Sciences, Bulgaria

Background. Antimalarial drug resistance has emerged as one of the greatest challenges facing malaria control today. Lack of alternatives and increasing ineffectiveness of the existing drugs are the main reasons for increased mortality and to combat this situations, new drugs are urgently needed. Therefore, series of chalones (1,3-diaryl-2-propen-1-ones) derivatives after in vitro screening were evaluated for in vivo antimalarial efficacy and immunomodulatory properties against malaria parasites.
Methods. Sixteen chalcones derivatives were screened for antimalarial activity under in vitro conditions on both chloroquine sensitive and chloroquine resistant strains of P. falciparum following WHO schizont maturation inhibition assay, in which three most potent were further evaluated in in vivo models for pharmacokinetic profile and antimalarial activity. Thirty six Balb/C mice of either sex were divided into six groups namely, a) contol, b)infected group, c)artemisnin treated (5mg/kg), d)Chalcone derivatives A41 (10mg/kg), e)AV21 (1omg/kg), f)AV27 (20mg/kg), all administered at single (oral/i.p)dose for consecutive five days, for evaluating several parameters, such as, parasitemia, temperature, body weight, organ weight, histology, ICAM-1, Nitric oxide and pro-inflammatory cytokines level before and after drug interventions.
Results. In vivo malaria models showed highly significant result at the fifth day of treatment with all the three chalcones A41 AV21 and AV27 as compared to non-treated group (p<0.001) in terms of parasitemia. Histology sections of spleen and liver reflects accumulation of more malaria pigment in non-treated group as compared to treated. Also, there was increased expression of cytokines (IL-1beta, TNF, IFN-gamma) and ICAM-1 level in non-treated mice as compared to treated. However, non-significant difference was observed in level of nitric oxide production on comparison of non-infected control and infected control with chalocne-treated groups.
Conclusions. The present study has shown the efficacy of at least 3 chalcone derivatives against malaria in vivo. There was also an increased expression of certain cytokines. Therefore, chalcones may be an adjunct to the treatment of resistant malaria infections.

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