IN-VITRO ANTIMALARIAL ACTIVITY BY SYBR GREEN-I BASED FLUORESCENCE ASSAY OF N-SUBSTITUTED PIPERAZINE DERIVATIVES SYNTHESISED BY HIGHER GREENER SOLVENTS AND IONIC LIQUIDS ON PLASMODIUM FALCIPARUM
Viraj P. Jatakiya*, Nadim M. R. Chhipa and Prof. Dr. Dhrubo Jyoti Sen
ABSTRACT
N-substituted novel piperazine derivatives in four series were planned to synthesize by comparison study for the solvents with higher greener values and lower greener values for that yield percentage and kinetic studies were performed and evaluated for their capacity to inhibit the growth of Plasmodium falciparum 3D7 strain in culture. N -ethyl piperazine has been conjugated with substituted aromatic acid chlorides in J-1 to J-3 series and in J-4 with higher homologous unsubstituted acid chloride and then converted in to Schiff’s base by substituted aromatic amines by conventional method (methanol) and green solvents (1-butanol and ionic liquid: triethyl methyl ammonium methyl sulphate). Rate of reaction was tested for all compounds by kinetic study and all compounds were characterized by spectral studies. The synthesised compounds have been screened by in-vitro method by SYBR Green-I assay for Plasmodium falciparum. Final compounds % yield in methanol was found around 88%, in 1-butanol around 66% and in ionic liquid above 99%. Overall rate of reaction was found 2nd order in kinetic study. Rate of reaction k in methanol was found = 0.0004 μg-1sec-1 and in 1-butanol it was = 0.0001 μg-1sec-1, half life of reaction was 50 seconds in methanol and 1000 seconds in 1-butanol while overall reaction time in ionic liquid was only 20 seconds. In antimalarial evaluation series J-3 (5-bromo-2- aminobenzoyl chloride series) was found to have highest activity in terms of IC50 (μM).(Compound J-33: 4-{-[(2-amino-5-bromophenyl)(4-ethylpiperazin-1-yl) methylidene] amino} benzene-sulfonamide) was found most active having IC50 0.076 μM and SI >2631.57. % yield and rate of reaction is highest in ionic liquid compared to other two solvents so reaction is more ecofriendly and more acceptable in this environmental benign solvent. Among all four series J-3 is more active and among all compounds J-33 is most active compounds against Plasmodium falciparum 3D7. So, the activities of compounds constitute a strong rationale for further investigation.
Keywords: Imidazolo-piperazine, Ethyl piperazine, Schiff’s base, Green solvents, Ionic liquid, Plasmodium falciparum 3D7 strain, SYBR Green-I assay, IC50, CC50, Selectivity Index.
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