DESIGN, SYNTHESIS, CHARACTERIZATION, ANTICANCER ACTIVITY AND IN SILICO ADME STUDY OF SOME NOVEL ALKYLTHIO TRIAZOLO THIADIAZOLE

Abstract: A sequence of 6-(6-(methylthio)-3-phenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole [5a], 6-(6-(ethylthio)-3-phenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole [5b], 3-phenyl-6-(propylthio)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole [5c] has been designed. The spectral analyses validated the synthesis of novel 6-(Alkylthio)-3-phenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole, which was examined using FT-IR, ¹H-NMR, ¹³C-NMR, and mass spectrometry. The ADME profiles demonstrated favorable oral bioavailability and pharmacokinetic characteristics. These parameters were investigated because many synthesized compounds often fail at later stages of drug discovery and development due to poor pharmacokinetic behavior. The SwissADME analysis provided theoretical insights into pharmacokinetics, revealing that most of the designed compounds exhibit high gastrointestinal absorption and do not cross the blood–brain barrier (BBB). This finding is particularly relevant for oral drugs targeting the gastrointestinal system, indicating their potential for good oral bioavailability. Overall, the newly synthesized compounds show promising pharmacokinetic properties, being well absorbed, distributed, metabolized, and excreted according to the SwissADME predictions. Therefore, these compounds may serve as viable candidates for further drug development. An in silico ADME evaluation was also conducted to assess their drug-likeness and support their potential as novel therapeutic agents. Anticancer evaluations demonstrated that the compounds had action against HepG2 and WRL68 cell lines. The synthesized chemical exhibited a pronounced cytotoxic impact on the HepG2 cell line (μg/mL 99.73), whereas little cytotoxicity was detected in normal human cells (WRL68 cell line).