In-Vivo and In-Vitro Biological Evaluation of Newly Synthesized 1,3,4-Thiadiazole Derivatives

Abstract

The present investigation was undertaken to evaluate the acute toxicity, dose selection and extensive biological screening of a series of synthesized 1,3,4-thiadiazole derivatives. Acute toxicity studies were carried out in experimental animals according to OECD guidelines, and the median lethal dose (LD₅₀) values were found to range between 750 and 1250 mg/kg. Based on these findings, one-tenth of the LD₅₀ was selected as the experimental dose for subsequent pharmacological evaluation, indicating a favorable safety profile for the tested compounds.The synthesized derivatives were screened for in-vivo analgesic, antipyretic and anti-inflammatory activities using standard experimental models. Several compounds exhibited significant pharmacological effects comparable to reference drugs. Compound IIIA10 showed potent analgesic and anti-inflammatory activity, while compound 2b demonstrated marked antipyretic efficacy, which was attributed to the presence of electron-withdrawing nitro and chloro substituents on the phenyl ring of the thiadiazole nucleus. Anti-inflammatory screening using the carrageenan-induced paw edema model revealed that compounds IIIA10, VA17, 2b and 3b produced significant inhibition of edema, suggesting effective suppression of inflammatory mediators.In-vitro antibacterial and antifungal activities were evaluated against selected Gram-positive, Gram-negative bacteria and fungal strains using the cup plate and MIC determination methods. Compounds 1b, 2b and 3b showed pronounced antimicrobial activity, highlighting the role of substituted phenyl rings and optimized lipophilicity in enhancing microbial inhibition. Antioxidant potential assessed by DPPH and nitric oxide scavenging assays revealed that compounds bearing hydroxyl and nitro substituents exhibited superior radical scavenging activity in a concentration-dependent manner.Overall, the results demonstrate that strategic substitution on the 1,3,4-thiadiazole scaffold significantly influences biological activity. The study identifies several lead molecules with promising safety and multifunctional pharmacological profiles, supporting further optimization and development of these derivatives as potential therapeutic agents.