Xavier, J.S.Karthikeyan, K.Ragavendran, V.NityanandaShetty, A.2026-02-052020Bioorganic Chemistry, 2020, 102, , pp. -452068https://doi.org/10.1016/j.bioorg.2020.104081https://idr.nitk.ac.in/handle/123456789/23746A new series of thiosemicarbazones were designed and synthesized. Their structures were confirmed by spectral characterization and single crystal XRD studies. Compounds MTSC-2 and ETSC-3 crystallized in the orthorhombic crystal system with space group Pbc2<inf>1</inf> andPca2<inf>1</inf>respectively. Density functional theory computational studies were performed on MTSC-2 and ETSC-3 along with natural bond orbital analysis and Mulliken population analysis to study the structural and electronic properties of the thiosemicarbazones. The HOMOs of the two thiosemicarbazones are ?5.2943 and ?5.1133 eV respectively while the LUMOs are ?1.6879 and ?1.6398 eV respectively. The energy gap is 3.6064 and 3.4736 eV respectively. Molecular docking studies were performed to determine the binding mode of the thiosemicarbazones against ?-tubulin. The theoretical studies were further supplemented with tubulin polymerization inhibition assay. All the four thiosemicarbazones proved effective in inhibiting the polymerization of ?- and ?-tubulin heterodimers into microtubules. The anticancer activity of these compounds showed their extreme potency against A549 and HepG2 cancer cell lines with IC<inf>50</inf> values of 0.051 – 0.189 µm and 0.042 – 0.136 µm respectively. Compound PTSC-4 showed the highest activity both against tubulin and the two cancer cell lines. This was in correlation with the theoretical studies. Hence, these four compounds, specifically PTSC-4, can be considered to be potential leads in the development of non-metallic anticancer agents. © 2020 Elsevier Inc.2 [4 [bis(2 hydroxyethyl)amino]benzylidene] n ethylhydrazine carbothioamide2 [4 [bis(2 hydroxyethyl)amino]benzylidene] n methylhydrazine carbothioamide2 [4 [bis(2 hydroxyethyl)amino]benzylidene] n phenylhydrazine carbothioamideantineoplastic agentbeta tubulinheterodimerthiosemicarbazone derivativetubulinunclassified drugantineoplastic activityArticlecarbon nuclear magnetic resonancecrystalcrystal structuredensity functional theoryhumanhuman cellIC50in vitro studymicrotubulemicrotubule assemblymolecular dockingpolymerizationpriority journalproton nuclear magnetic resonancequantum mechanicsspectroscopysynthesistubulin polymerization assayX ray crystallographyX ray diffractionchemical structuredrug designproceduresstructure activity relationAntineoplastic AgentsDrug DesignHumansMolecular Docking SimulationMolecular StructureStructure-Activity RelationshipThiosemicarbazonesTubulin