Synthesis and Toxicity Evaluation of Some N(4)-Aryl Substituted 5-Trifluoromethoxyisatin-3-thiosemicarbazones

Pervez, Humayun; Saira, Naveeda; Iqbal, Mohammad Saeed; Yaqub, Muhammad; Khan, Khalid Mohammed

A series of twenty one N(4)-aryl substituted 5-trifluoromethoxyisatin-3-thiosemicarbazones 3a-3u was synthesized by the reaction of trifluoromethoxyisatin 1 with different arylthiosemicarbazides 2 in aqueous ethanol (50%), containing a few drops of acetic acid. Their structures were established on the basis of analytical (CHN) and spectral (IR, (1)H-NMR, EIMS) data. All the synthesized compounds were evaluated for their toxicity potential by a brine shrimp lethality bioassay. Ten compounds i.e., 3a, 3e, 3i-3l and 3n-3q proved to be active in this assay, displaying promising toxicity (LD(50) = 1.11 × 10(−5) M − 1.80 × 10(−4) M). Amongst these, 3k, 3n and 3o were found to be the most active ones (LD(50) = 1.11 × 10(−5) M − 1.43 × 10(−5) M). Compound 3k showed the highest activity with a LD(50) value of 1.11 × 10(−5) M and can, therefore, be used as a lead for further studies. Structure-activity relationship (SAR) studies revealed that the presence of strong inductively electron-attracting trifluoromethoxy substituent at position-5 of the isatin moiety played an important role in inducing or enhancing toxic potentiality of some of the synthesized compounds.