TY - JOUR

T1 - 6-(4′-Aryl-1′,2′,3′-triazolyl)-spirostan-3,5-diols and 6-(4′-Aryl-1′,2′,3′-triazolyl)-7-hydroxyspirosta-1,4-dien-3-ones

T2 - Synthesis and analysis of their cytotoxicity

AU - Mironov, Maxim E.

AU - Oleshko, Olga S.

AU - Pokrovskii, Mikhail A.

AU - Rybalova, Tatyana V.

AU - Pechurov, Vladislav K.

AU - Pokrovskii, Andrey G.

AU - Cheresis, Sergey V.

AU - Mishinov, Sergey V.

AU - Stupak, Vyacheslav V.

AU - Shults, Elvira E.

N1 - Publisher Copyright: © 2019

PY - 2019/11/1

Y1 - 2019/11/1

N2 - In an endeavour to develop potent anti-tumor agents from diosgenin, a series of C-6 derived 1,2,3-triazolyl derivatives were designed and synthesized by employing Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition reaction of novel azides – (22R,25R)-6β-azidospirostan-3β,5α-diol and 6β-azido-7α-hydroxyspirosta-1,4-dien-3-one with aryl(hetaryl)alkynes. All the derivatives were evaluated for cytotoxic activity by MTT assay against eight different human cancer cell lines: T-cellular leucosis (CEM-13), human monocytes (U-937), breast (MDA-MB-231, BT-474), prostate (DU-145) and glioblastoma (U-87MG, SNB-19, T98G). The results of this study suggested that 6-(4′-aryl-1′,2′,3′-triazolyl)spirostan-3,5-diols 2, 3, 4, 5 and 6 possessed a promising cytotoxic potential. The corresponding 6-substituted 7-hydroxy-1,4-spirostadien-3-ones shown less cytotoxity on the human cancer cells. Compounds 2, 3, 4, and 5 which demonstrated high grown inhibition against glioma cancer cells U-87 and T98G, and also on the human-derived N118669 primary glioblastoma cell line (with GI50 values in the range of 5–9 μM), were not affected the growth of SNB-19 cells. The data revealed that phenyl, 4-methoxyphenyl, 4-fluorophenyl, 3,4,5-trimethoxyphenyl or 2-pyridinyl substituent in the triazole moiety at the C-6 position significantly improved the anti-tumor activity. The mentioned position at the spirostan core may be favourable for the synthesis of potent anticancer leads from diosgenin.

AB - In an endeavour to develop potent anti-tumor agents from diosgenin, a series of C-6 derived 1,2,3-triazolyl derivatives were designed and synthesized by employing Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition reaction of novel azides – (22R,25R)-6β-azidospirostan-3β,5α-diol and 6β-azido-7α-hydroxyspirosta-1,4-dien-3-one with aryl(hetaryl)alkynes. All the derivatives were evaluated for cytotoxic activity by MTT assay against eight different human cancer cell lines: T-cellular leucosis (CEM-13), human monocytes (U-937), breast (MDA-MB-231, BT-474), prostate (DU-145) and glioblastoma (U-87MG, SNB-19, T98G). The results of this study suggested that 6-(4′-aryl-1′,2′,3′-triazolyl)spirostan-3,5-diols 2, 3, 4, 5 and 6 possessed a promising cytotoxic potential. The corresponding 6-substituted 7-hydroxy-1,4-spirostadien-3-ones shown less cytotoxity on the human cancer cells. Compounds 2, 3, 4, and 5 which demonstrated high grown inhibition against glioma cancer cells U-87 and T98G, and also on the human-derived N118669 primary glioblastoma cell line (with GI50 values in the range of 5–9 μM), were not affected the growth of SNB-19 cells. The data revealed that phenyl, 4-methoxyphenyl, 4-fluorophenyl, 3,4,5-trimethoxyphenyl or 2-pyridinyl substituent in the triazole moiety at the C-6 position significantly improved the anti-tumor activity. The mentioned position at the spirostan core may be favourable for the synthesis of potent anticancer leads from diosgenin.

KW - Click chemistry

KW - Cytotoxicity

KW - Diosgenin

KW - Spirostanes

KW - Steroids

KW - APOPTOSIS

KW - STEROIDS

KW - SAPONINS

KW - DIOSGENIN

KW - BIOLOGICAL EVALUATION

KW - CELL-CYCLE ARREST

UR - http://www.scopus.com/inward/record.url?scp=85069903351&partnerID=8YFLogxK

U2 - 10.1016/j.steroids.2019.108460

DO - 10.1016/j.steroids.2019.108460

M3 - Article

C2 - 31344410

AN - SCOPUS:85069903351

VL - 151

SP - 108460

JO - Steroids

JF - Steroids

SN - 0039-128X

M1 - 108460

ER -