Pyrazolines show different biological activities. In recent years, interest in the chemistry of hydrazonoyl halides has been renewed. 1,3,4-Thiadiazoles are one of the most common heterocyclic pharmacophores with a wide range of biological activities. Ethyl 2-(5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-methyl-thiazole-5-carboxylate, 2-(5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one, and 1-(2-(5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-methylthiazol-5-yl)ethan-1-one were synthesized from the reaction of 5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide with different halogenated compounds. Thiazole, 1,3,4-thiadiazole and pyrano[2,3-d]thiazole derivatives were also synthesized. The structures of the newly synthesized compounds were elucidated based on elemental analysis, spectral data, and alternative synthetic routes whenever possible. Additionally, the newly synthesized compounds were screened for antimicrobial activity against various microorganisms. A new series of novel functionalized 1,3,4-thiadiazoles, 1,3-thiazoles, and pyrazoline-containing moieties were synthesized using hydrazonoyl halides as precursors and evaluated for their in vitro antibacterial, and antifungal activities. The antimicrobial results of the examined compounds revealed promising results and some derivatives have activities similar to the references used.

Green synthesis using L-proline as an organocatalyst is crucial due to its reusability, mild conditions, clean reactions, easy workup, high purity, short reaction times, and high yields. However, existing methods often involve harsh conditions and longer reaction times. In this study, 2-cyano-N’-(2-cyanoacetyl)acetohydrazide (3) was prepared and condensed with various benzaldehyde derivatives to yield 2-cyano-N’-(2-cyano-3-phenylacryloyl)-3-phenylacrylohydrazide derivatives (5a–e, 7a,b) using a grinding technique with moist L-proline. Additionally, three 2-cyano-N’-(2-cyano-3-heterylbut-2-enoyl)-3-heterylbut-2-enehydrazides (9, 11, 13) were synthesized by condensing compound 3 with respective (heteraryl)ketones (8, 10, 12) following the same method. The synthesized compounds were characterized using IR, NMR, and MS spectroscopy. L-proline’s reusability was confirmed for up to four cycles without significant yield loss, showcasing the protocol’s efficiency and sustainability. The new compounds were screened for anticancer activities against the HCT-116 colon carcinoma cell line using the MTT assay. Molecular docking studies revealed the binding conformations of the most potent compounds to the target protein (PDB ID 6MTU), correlating well with in vitro results. In silico ADMET analysis indicated favorable pharmacokinetic properties, highlighting these novel compounds as promising targeted anti-colon cancer agents.