Pyridine Thiosemicarbazones as Anticancer and Antimicrobial Agents: A Promising Class of Low‐Toxicity Therapeutics

ABSTRACT In vitro anticancer and antimicrobial activities of 24 pyridine thiosemicarbazone (PTSC) derivatives ( 3a–3x ), synthesized via a two‐step process starting from hydrazine hydrate and carbon disulfide, have demonstrated promising results. Five compounds 3 g , 3 h , 3v , 3w , and 3x exhibited significant anticancer activity at a concentration of 10 µM against several cancer cell lines, including leukemia (CCRF‐CEM and MOLT‐4), melanoma (SK‐MEL‐2 and SK‐MEL‐5), and breast cancer (MDA‐MB‐468), with growth percentage values ranging from ‐11.61% to ‐75.49%. Among these, compound 3w displayed exceptional anticancer efficacy against the renal cancer cell line UO‐31, with a GI₅₀ value of 0.57 µM, while showing no cytotoxicity toward normal cells (lethal concentration 50% > 100 µM). Further in vitro evaluations using ovarian (IGROV1), colon (HCC‐2998), and melanoma (MALME‐3 M) cancer cell lines revealed that compounds 3 g , 3 h , and 3w exhibited GI₅₀ values ranging from 2.00 to 4.89 µM, supporting their cytotoxic potential. Notably, compounds 3 g , 3 h , 3w , and 3x were found to be more potent than the reference drug, Sunitinib . These findings highlight the therapeutic potential of PTSC derivatives and underscore their promise as lead compounds in anticancer drug development. Additionally, all PTSC derivatives were evaluated for antimicrobial efficacy against five different Gram‐positive and Gram‐negative bacterial strains and two fungal pathogens at a concentration of 32 µg/mL. Among them, compound 3q exhibited the highest growth inhibition (GI) of 97.63% against Acinetobacter baumannii , without exhibiting any toxicity toward human embryonic kidney (HEK‐293) cells and human red blood cells at concentrations ranging from 32 to 0.25 µg/mL. Furthermore, compounds 3o , 3k , and 3x demonstrated in vitro GI percentages of 53.24%, 77.67%, and 95.77%, respectively, against Candida albicans . These results support the potential of PTSC derivatives as multifunctional therapeutic agents with both anticancer and antimicrobial properties.