Synthesis and biological activity of hydrazones of 5α-steroids.

Condensation reactions catalyzed by acetic acid of severalarylhydrazine (2,4-dinitrophenyl hydrazine) and hydrazides (hydrazides of bromobenzoic and salicylic acid, benzofuran-2- and indol-2-carboxylicacid) with 3β-acetoxy- and 3β-hydroxy-5α-pregn-16-en-20-one (1 and 2), epiandrosterone (6) and 5α-androst-2-en-17- one (9) were studied for the purpose of synthesizing potentially bioactive 5-steroidal hydrazones. The starting ketones (1,2,6,9) were synthesized on the bases of aglicon of steroidal saponine - tigogenin isolated from plant “Yucca gloriosa” introduced in Georgia. The structures of synthesized new hydrazones (3-5,7,8,10,11) were established by NMR 1H, 13C and mass-spectral data. The antiviral activity some of them (7,8,10,11) were studied

Synthesis of some 5α-androstano[17,16-d]pyrazoles from tigogenin

Condensation reaction of several arylhydrazines with 16α, 17α-epoxy-5α-pregnan-3β-ol-20-one synthesized from 5α-pregn-16-en-3β-ol-20-one–intermediate product of tigogenin transformation – were studied for the purpose of synthesizing potentially bioactive 5α-androstano [17,16-d] pyrazoles. Despite various conditions (different temperature, in protic and aprotic solvents) of the reaction, a complex mixture was obtained and then separated by column chromatography (eluent-hexane-ethylacetate). Two main products of intermolecular cyclization: 5α-androstano [17,16-d] pyrazole and its hydrogenated analogue – 5α-androstano [17,16-d]pyrazolines were isolated by substitution of electron-donating group (phenylhydrazine, p-methyl-, p-bromophenylhydrazine) at the hydrazine amine atom. In the presence of electron-withdrawing group (p-nitrophenylhydrazine) at the hydrazine amine atom cis-opening product of epoxygroup – 16α-acetoxy-5α-pregnan-3β, 17α-diol-20-one hydrazine – was obtained. The structures of synthesized compounds were established by NMR1H,13C and mass-spectral data. Structures of 3β-hydroxy-1/-phenyl-3/-methyl-5α-androstano [17,16-d] pyrazoles were confirmed by IR, NMR1H,13C, DEPT-135, HMBC and mass-spectral data. Synthesis of 5α-androstano [17,16-d] pyrazolines with 5α-androstano [17,16-d] pyrazoles by condensation reactions in the mentioned conditions was not described previously

Synthesis of New 5α-Steroidal Hydrazones from Tigogenin

In the present study potentially biologically active steroids, new hydrazones, semicarbazones, and 20O-methyloxime have been synthesized from ketones of the 5α-pregnene, 5α-pregnane, and 5αandrostane series. The condensation reaction of ketones – 5α-pregn-16-en-3β-ol-20-one, 5α-pregnan3β-ol-20-one and 5α-androstan-3β-ol-17-one – with various arylhydrazides, semicarbazide, and methoxyamine was carried out in ethanol with a catalytic amount of acetic acid. The starting ketones were made from tigogenin, an aglycone of steroidal saponins that is a domestic raw material for the synthesis of 5α-series steroids. Tigogenin was isolated from the Yucca gloriosa plant, which was introduced in Georgia.1H,13C NMR and mass spectra were used to confirm the structure of the newly obtained steroids. The cytotoxicity of these and previously synthesized hydrazones was investigated in vitro using the Rezazurin reduction test and Hoechst test aginst lung carcinoma (A549), colorectal adenocarcinoma (DLD-1) and normal skin fibroblasts (WS-1) cell lines in comparison to etoposide. The results show that, of all the compounds studied, only p-methyl-and pmethoxybenzoylhydrazone 5α-pregnan-3β-ol-20-one are of particular interest since, unlike the others, they demonstrate activity comparable to etoposide

Novel antimicrobial agents' discovery among the steroid derivatives.

Fourteen steroid compounds were in silico evaluated using computer program PASS as antimicrobial agents. The experimental studies evaluation revealed that all compounds have good antibacterial activity with MIC at range of 0.003-0.96 mg/mL and MBC 0.06-1.92 mg/mL. Almost all compounds except of compound 4 (3β-acetoxy-1/-p-chlorophenyl-3/-methyl-5α-androstano[17,16-d]pyrazoline) were more potent than Ampicillin, and they were equipotent or more potent than Streptomycine. All compounds exhibited good antifungal activity with MIC at 0.003-0.96 mg/mL and MFC at 0.006-1.92 mg/mL but with different sensitivity against fungi tested. According to docking studies 14-alpha demethylase inhibition may be responsible for antifungal activity. Prediction of toxicity by PROTOX and GUSAR revealed that compounds have low toxicity and can be considered as potential lead compounds for the further studies