Synthesis, characterization, computational studies and in vitro antiparasitic activity of novel flavanoidal-1,2,4,5-tetrazinane-6'-thione.

Keeping in view the growing resistance of conventional antiparasitic drugs, this study aimed to synthesize a series of six noble flavanoidal tetrazinane-6'-thione derivatives by employing a facile one pot reaction pathway. Structural characterizations of synthesized compounds were performed by using IR, 1 HNMR, 13 CNMR and LC-MS spectra. Molecular docking study showed that one of the newly synthesized compounds strongly bind with the amino residues of BSA with two hydrogen bonding interactions. Physiological properties, pharmacokinetic properties (ADME) and toxicity of all synthesized compounds was carried out using Molinspiration and pkCSM softwares. DFT calculations were performed for all synthesized compounds using B3LYP method to obtain various molecular properties. Using a previously established model for parasitic infections, Clinostomum complanatum we showed that the newly synthesized compounds have a very potent parasitic activity. To elucidate the possible mechanisms, we tested the exposed parasites and observed a perturbation in lipid peroxidation and the antioxidant enzyme superoxide dismutase. Implications of this are discussed in the light of development of these molecules as antiparasitic drugs. HIGHLIGHTSSix noble flavanoidal-1,2,4,5-tetrazinane-6'-thiones (7-12) were synthesized using flavanone derivatives and thiocarbohydrazide in acetic acid as a reagent in ethanol employing one-pot synthesis.Structural characterization of synthesized compounds was done using IR, 1 HNMR, 13 CNMR and LC-MS spectra.Physicochemical analysis determined that all synthesized compounds are efficiently absorbed and have good permeability. In silico ADME and Toxic properties were determined for all synthesized compounds.In vitro antiparasitic activity was performed for all synthesized compounds against Clinostomum complanatum .Molecular Docking studies demonstrated the binding interaction with BSA enzyme through hydrogen bonding.Density functional theory (DFT) have been performed to estimate the various molecular properties of the synthesized compounds.Communicated by Ramaswamy H. Sarma.