A method for the synthesis of 5-phenyl-1,3-thiazole-4-sulfonyl chloride was developed based on the cyclization of ethyl 2-{[1-(benzylsulfanyl)-2-oxo-2-phenylethyl]amino}-2-oxoacetate obtained from available reagents under the action of the Lawesson’s reagent and oxidative chlorination of the intermediate benzyl 5-phenyl-1,3thiazol-4-ylsulfide. The resulting sulfonyl chloride was converted into a series of 5-phenyl-1,3-thiazole-4-sulfonamide derivatives for which in vitro antitumor activity screening studies were performed on 60 cancer cell lines.

A thirteen 4-cyano-2-phenyl-1,3-oxazole-5-sulfonamide analogs have been synthesized and characterized by spectroscopy methods, elemental analysis. Their growth inhibiting activity was determined in vitro in the one dose assay against the total NCI-60 human cancer cell line panel. The five-dose analysis was performed on the six compounds with greater cytotoxicity. Two compounds 8 and 9 exhibited the greatest potency against total NCI-60 cancer cell lines in the five dose assay. Furthermore, compound 9 with 3-methylpiperidine fragment turned out to be two times more active than compound 8 with 4-methylpiperidine (GI50 = 1.4±0.1 against 2.5±0.4, GI = 3.9±0.6 against 7.1±1.3 and LC50 = 7.1±1.0 against 16.4±2.3 µM). The lack of commonly used drugs that show a high correlation with the majority of analyzed compounds, based on two out of three calculated parameters of anticancer potency, suggests that they may interact with a unique target. The ADMET analysis results predict that this compound meets the drug similarity criteria and does not belong to interfering molecules that react non-specifically with numerous targets. The prediction of lead likeness for all compounds is also included, meaning that any of them can be optimized to enhance selectivity and other pharmacological properties that characterize their chemotherapeutic potential

Sulfonylated 5-piperazine-substituted 1,3-oxazole-4-carbonitriles were synthesized and evaluated for in vitro anticancer activity. Cytotoxicity was assessed in hepatocellular (HepG2, Huh7), breast (MCF-7, MDA-MB-231), cervical (HeLa), melanoma (M21), and neuroblastoma (Kelly, SH-SY5Y) cell lines, with HEK293 cells used as a non-malignant control. Compounds 7a, 7b, and 8aa emerged as lead structures. Notably, compound 7b showed the highest activity in Kelly neuroblastoma cells (IC₅₀ = 1.3 µM) while exhibiting low cytotoxicity toward HEK293 cells (IC₅₀ > 10 µM), indicating an improved selectivity profile relative to doxorubicin. In silico molecular docking suggested favorable interactions of the lead compounds with several cancer-associated proteins, with the highest predicted affinity observed for Aurora A kinase, along with additional predicted interactions with cyclin-dependent kinases. Predicted ADMET properties of compounds 7a, 7b, and 8aa compared favorably with doxorubicin, although the lead compounds were not readily biodegradable under OECD 301D conditions. Overall, these findings identify oxazole-4-carbonitriles as promising anticancer candidates with a putative kinase-directed mechanism of action.

The discovery of nucleoside antibiotics gave impetus to the development of the chemistry of pyrrolo[2,3-d]pyrimidines and thieno[2,3-d]pyrimidines as biologically active compounds. This work describes a universal and efficient approach to the synthesis of new pyrrolo[2,3-d]pyrimidine and thieno[2,3-d]pyrimidine derivatives of piperazin-1-yl-1,3-oxazole-4-carbonitriles. Their potential as biologically active compounds is considered and ADMET-score is predicted to assess their further application as pharmaceutical substances

Neuroblastoma, a leading cause of pediatric cancer mortality, requires efficient and selective therapeutics. We synthesized and characterized a series of sulfonated 5-piperazine-containing 1,3-oxazole-4-carbonitrile derivatives via sulfonylation protocols and evaluated their in vitro cytotoxicity against human hepatocellular carcinoma (HepG2, Huh7), breast (MCF7, MDA-MB-231), cervical (HeLa), melanoma (M21), and two neuroblastoma (Kelly, SHSY5Y) cell lines, alongside non-malignant HEK293 cells. Three compounds (7a, 7b, and 8aa) demonstrated efficient and selective cytotoxicity toward MYCN-amplified (Kelly) and MYCN-non-amplified (SHSY5Y) neuroblastoma cells, with 7b being the most active (IC₅₀ = 1.9 µM in Kelly cells) and showing minimal toxicity in HEK293 (IC₅₀ > 10 µM). In Kelly cells, 7b matched doxorubicin while showing lower off-target toxicity and low-micromolar activity in solid tumors. The hit compounds were shown to be not readily biodegradable under OECD 301D test. In silico docking revealed high-affinity binding to the ATP-binding site of Aurora A kinase in the Aurora A/N-MYC complex (ΔG = –10.8 to –10.9 kcal/mol). Compound 7b exhibited broad cytotoxicity across all tested cancers (IC₅₀ = 1.5–4.0 µM). ADMET profiling of 7a, 7b, and 8aa indicated favorable pharmacokinetic and toxicity parameters compared with doxorubicin. These findings identify sulfonylated oxazole-4-carbonitriles as neuroblastoma therapeutics with potential use against proliferating malignancies.