Synthesis, crystal structure, computational investigation, molecular docking analysis and anti-lung cancer activity of novel (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one

Abstract

Ever since the disease of cancer was discovered, man has been mystified by both its mysterious origin and the even more mystifying mechanisms by which it spreads. Although advances in surgery and radiotherapy have significantly impacted cancer treatment, the idea of systemic chemotherapy which is targeted specifically at cancer cells and has minimal side effects remains a strategic goal for the future. A novel thiazolidin-4-one analogue was synthesized by the reaction of 1,2,4,5-tetraazaspiro[5.5]undecane-3-thione with chloroacetic acid. The newly synthesized compound was investigated theoretically as well as experimentally by FT-IR, 1H, 13C NMR and UV–Vis spectra and biologically screened in vitro for its anti-lung cancer activity against A549 cancer cell line. The crystal structure of (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one has been determined by single crystal X-ray diffraction and revealed that it belongs to monoclinic system with cell dimensions: a = 18.9393 (16) Å, b = 5.2747 (4) Å, c = 10.9518 (9) Å, α = 90°, β = 90.214 (3), γ = 90° and V = 1082.85 (15) Å3. Hirshfeld surface analysis was performed to study the nature of intermolecular interactions within the crystal structure via 3D and 2D fingerprint surfaces and to demonstrate H-bonding with close contacts in crystal via dnorm surface. A descriptive study of (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one was done by using density functional theory at DFT/B3LYP/6–311 ++G (d,p) basis set. Results of NLO analysis, ELF, LOL, NCI, AIM, HOMO-LUMO, first hyperpolarizability and molecular electrostatic potential were reported. Theoretical calculation of ADMET properties suggested that the synthesized compounds have a good pharmacokinetic profile. The results of cytotoxic evaluation indicated that (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one has broad-spectrum cytotoxic activity with IC50 values of 240 μM against Human lung carcinoma cell line (A549).