SYNTHESIS AND ANTIMALARIAL ACTIVITY OF SOME NEW 3-PHENYL-2-THIOXOTHIAZOLIDIN-4-ONE DERIVATIVES
Objective: Current therapies to treat P. falciparum malaria are heavily reliant on artemisinin-based combinations. However, resistance to artemisinin has recently been identified, and resistance to key artemisinin partner drugs is already widespread. Therefore, there is an urgent need for new antimalarial drugs with improved attributes over older therapies. The objective of this research work is to synthesize new antimalarial agents more effective against clinically relevant malarial strains.
Methods: In present work, a series of ten 3-phenyl-2-thioxothiazolidin-4-one (MF1-MF10) derivatives, were synthesized by Knoevenagel condensation of N-phenyl rhodanine (I1) with substituted aromatic or hetro aromatic aldehydes using microwave irradiation. N-phenyl rhodanine (I1) was synthesized by a conventional reaction involving methyl-2-mercaptoacetate (1) and phenyl Isothiocyanates in presence of triethylamine. All the synthesized compounds were characterized by various spectroscopic techniques and evaluated for in-vitro antimalarial activity by microdilution technique against resistance strains of Plasmodium falciparum.
Results: The antimalarial activity data showed that six compounds (MF1, MF3, MF4, MF5, MF7 and MF8) exhibited IC50 values ranging from 1.0-1.30 Âµg/ml, three compounds (MF2, MF6 and MF10) displayed IC50 values in the range of 0.9-1.0 Âµg/ml. Compound MF9 showed most significant result with maximum activity (IC50 = 0.85Âµg/ml).
Conclusion: The antimalarial activity results revealed that compound MF9 possess potent activity and could be identified as a promising lead for further investigation.
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