Steroidal dihydrocarbothioic acid amido pyrazoles: synthesis, characterization, cytotoxicity and genotoxicity studies

Abstract

A new series of steroidal dihydrocarbothioic acid amido pyrazole analogues were synthesized, and after characterization, evaluation for cytotoxicity, comet assay and western blotting was carried out. The synthesis of these analogues is convenient and involves two steps, i.e. aldol condensation as first step followed by nucleophilic addition of thiosemicarbazide across α, β-unsaturated carbonyl as a later step. Quantitative yields of more than 80 % are obtained in both the steps. After characterization by IR, (1)H NMR, (13)C NMR, MS and analytical data, all the compounds of both series were tested for cytotoxic activity against a panel of different human cancer cell lines by MTT assay, during which compound 3e, 3f, 4e, 4f and 4h are very potent especially against HepG2 and MCF-7 cancer cell lines. Cell cycle analysis depicted the cell death in S-phase while as annexin V-FITC/PI analysis showed that compounds effectively induce apoptosis. Apoptotic degradation of DNA of MCF-7 cells in the presence of different steroidal derivatives was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). In western blotting analysis, the relative expressions of relevant apoptotic markers depicted an apoptosis by steroidal dihydropyrazole in MCF-7 cancer cells.

L‐Proline Catalyzed Synthesis of Steroidal Pyridones And Their DFT Studies

“…The reaction did not progress at room temperature with or without catalyst except L-proline, however, upon heating at 70 °C in the presence of inorganic bases like Na 2 CO 3 /K 2 CO 3 , 5 a was formed in low yield (Table 1, entries 9, 10), making these bases less suitable for producing desired products. While moderate yields were obtained when the reaction was carried out in other bases like NaOEt, Et 3 N, piperidine, and DBU (Table 1, entries [11][12][13][14]. Moreover, when Lproline was used as a catalyst, the yield of desired product 5 a was increased upto 85 % (Table 1, entries 15, 24).…”

“…[5] For example, heterosteroids like Finasteride [6] (5α-reductase inhibitor), Formestane (aromatase), [7] Abiraterone, and Exemestane (anticancer drug), [7,8] and Pipecuronium (neuromuscular junction blocking agent) (Figure 1). [9] Considering these biological activities shown by heterosteroids, efforts are continuously being made by medicinal chemists to annelate A and D rings of steroidal molecules with various heterocycles such as pyridine, [10] pyrimidine, [11] pyrazole, [12] pyrrole, oxazoline, [13] or isoxazole using different synthetic methodologies (Figure 2). [14] In addition to being used in the synthesis of peptides, [15][16][17] 2-pyridones serve as an important core unit in a wide variety of drugs, agrochemicals, and functional materials.…”

“…Considering these biological activities shown by heterosteroids, efforts are continuously being made by medicinal chemists to annelate A and D rings of steroidal molecules with various heterocycles such as pyridine, [10] pyrimidine, [11] pyrazole, [12] pyrrole, oxazoline, [13] or isoxazole using different synthetic methodologies (Figure 2). [14] …”

CFL light promoted one-pot synthesis of pyrano[3,2-c]chromen-5(4H)-ones

“…Unique chemical, [1] biological, [2] and physical properties [3] associated with pyran derivatives have found broad applications as agrochemical and drugs. Pyran derivatives are widespread in nature.…”