Browsing by Author "Hristova R."

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    Novel methyl-substituted pyrrole hydrazones as selective melanoma agents
    (2025-01-01) Vladimirova S.; Hristova R.; Iliev I.
    Melanoma represents the most aggressive form of skin cancer, derived from melanocytes − the pigment-producing cells located in the epidermis. Effective treatment of melanoma remains a major clinical challenge, largely due to its capacity for immune evasion, rapid metastatic spread, and the development of resistance to therapeutic interventions. Based on our previously developed compounds with high selectivity towards melanoma SH-4 cell line, we created a new series of compounds in which we replaced the halogen atom with a methyl group in the precursor pyrrole-based carbohydrazide 2 . All derivative hydrazones ( 2A–D ) were synthesized by the condensation of carbohydrazide 2 with various substituted pyrrole aldehydes, subsequently characterized, and subjected to detailed spectroscopic analysis. In vitro evaluation of these newly developed compounds was performed across a diverse set of cancerous and non-cancerous cell lines to determine their biological effects. A safety profile was established using the BALB 3 T3 NRU-assay with mouse embryonic fibroblasts (BALB 3 T3 clone A31), revealing minimal cytotoxicity and an absence of phototoxic effects. Antiproliferative effects were quantified in keratinocytes (HaCaT) and melanoma (SH-4) cells using the MTT dye reduction assay. Of particular note, compound 2C emerged as the most selective agent (SI = 5.51) against human melanoma cells, displaying significant antiproliferative activity (IC50 = 31.93 ± 2.59). Further investigation revealed that the cytotoxic action of 2C is mediated by the induction of cell accumulation in the S/G2 phase. Consistent with our prior research, the current results further confirm that hydrazones synthesized via condensation with β-aldehydes exhibit enhanced bioactivity relative to those obtained from α-aldehydes.