title: Synthesis and Toxicity Evaluation of Some N4-Aryl Substituted 5-Trifluoromethoxyisatin-3-thiosemicarbazones.
abstract: A series of twenty one N4-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, 1H-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 (LD50 = 1.11 × 10-5 M - 1.80 × 10-4 M). Amongst these, 3k, 3n and 3o were found to be the most active ones (LD50 = 1.11 × 10-5 M - 1.43 × 10-5 M). Compound 3k showed the highest activity with a LD50 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.
authors.affiliation: Department of Chemistry, Bahauddin Zakariya University, Multan-60800, Pakistan. pdhpervez@hotmail.com.
authors.forename: Humayun
authors.initials: H
authors.lastname: Pervez
authors.affiliation: Department of Chemistry, Bahauddin Zakariya University, Multan-60800, Pakistan.
authors.forename: Naveeda
authors.initials: N
authors.lastname: Saira
authors.affiliation: Department of Chemistry, FC College, Lahore-54600, Pakistan.
authors.forename: Mohammad Saeed
authors.initials: MS
authors.lastname: Iqbal
authors.affiliation: Department of Chemistry, Bahauddin Zakariya University, Multan-60800, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yaqub
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
mesh_terms: D000818:Animals; D001156:Artemia / Q000187:drug effects; D001681:Biological Assay; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D013882:Thiosemicarbazones