Synthesis, crystal structure analysis, computational modelling and evaluation of anti-cervical cancer activity of...

Thiocarbazones are widely used as bioactive and pharmaceutical intermediates in medicinal chemistry and have been shown to exhibit diverse biological and pharmacological activities such as antimicrobial, anticancer, anti-viral, anti-convulsant and anti-inflammatory etc. In continuation of our interest in biologically active heterocycles and in an attempt to synthesize a spiro derivative, 1,2,4,5-tetraazaspiro[5.7]tridecane-3-thione, herein, the synthesis of 1,5-dicyclooctyl thiocarbohydrazone (3) has been reported via reaction of the cyclooctanone and thiocarbohydrazide. The structure was assigned on the basis of detailed spectral analysis and also confirmed by X-ray crystal studies. The Hirshfeld surface analysis indicates that the most significant interaction is S⋯H (12.7%). The presentation of mechanistic aspects regarding the plausible route of its formation has also been included. The first hyperpolarizability (β₀) was found to be 10.22 × 10^-30 esu, which indicates that the compound exhibits good non-linear optical properties. The density functional theory (DFT) method has been used to characterize the spectroscopic properties and vibrational analysis of 1,5-dicyclooctyl thiocarbohydrazone (3) theoretically. The compound and cisplatin (standard) were screened for their antiproliferative activity against the human cervical cancer cell line (SiHa) and they exhibited significant activity with IC₅₀ values of 250 μM and 15 μM, respectively. The inhibitory nature of the title compound against viral oncoprotein E6 was confirmed by studies using molecular docking analysis. The results of biological activity and in silico analysis indicate that the synthesized molecule could act as a precursor for the synthesis of new heterocyclic derivatives of medicinal importance.