- Synthesis of new symmetrical bis-steroidal pyrazine analogues from diosgenin
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New symmetrical bis-steroidal pyrazine dimers that are cephalostatins/ ritterazines analogues have been prepared easily from a cheap, readily available natural steroid (diosgenin). These dimers were obtained by classical, condensation of α-amino ketones in order to construct the pyrazine rings. The three dimers differ in the functionalized diosgenin: (25R)-5α,6β- dihydroxy-5α-spirosta-3-one, (25R)-4,5α-epoxy-5β-spirosta-3,6- dione and (25R)-5α-hydroxy-5α-spirosta-3,6-dione respectively.
- Shawakfeh, Khaled Q.,Al-Said, Naim H.
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- Antiproliferative, cytotoxic, and apoptotic activity of steroidal oximes in cervicouterine cell lines
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Steroidal sapogenins have shown antiproliferative effects against several tumor cell lines; and their effects on human cancer cells are currently under study. Changes in the functionality on the steroidal structure make it possible to modify the biological activity of compounds. Herein, we report the synthesis and in vitro antitumor activity of two steroidal oxime compounds on cervical cancer cells. These derivatives were synthesized from the steroidal sapogenin diosgenin in good yields. The in vitro assays show that the steroidal oximes show significant antiproliferative activity compared to the one observed for diosgenin. Cell proliferation, cell death, and the cytotoxic effects were determined in both cervical cancer cells and human lymphocytes. The cancer cells showed apoptotic morphology and an increased presence of active caspase-3, providing the notion of a death pathway in the cell. Significantly, the steroidal oximes did not exert a cytotoxic effect on lymphocytes.
- Sánchez-Sánchez, Luis,Hernández-Linares, María Guadalupe,Escobar, María L.,López-Mu?oz, Hugo,Zenteno, Edgar,Fernández-Herrera, María A.,Guerrero-Luna, Gabriel,Carrasco-Carballo, Alan,Sandoval-Ramírez, Jesús
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- Synthesis of bis-diosgenin pyrazine dimers: New cephalostatin analogs
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A convenient synthesis for bis-diosgenin pyrazine dimers, cephalostatin analogues is reported. These symmetrical dimeric steroid-pyrazines were obtained by the classical condensation of α-amino ketones, the most efficient method for pyrazine ring construction.
- Shawakfeh, Khaled Q.,Al-Said, Naim H.,Al-Zoubi, Raed M.
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- Diosgenone synthesis, anti-malarial activity and QSAR of analogues of this natural product
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Solanum nudum Dunal steroids have been reported as being antimalarial compounds; however, their concentration in plants is low, meaning that the species could be threatened by over-harvesting for this purpose. Swern oxidation was used for hemisynthesis of diosgenone (one of the most active steroidal sapogenin diosgenin compounds). Eighteen structural analogues were prepared; three of them were found to be more active than diosgenone (IC50 27.9 μM vs. 10.1 μM, 2.9 μM and 11.3 μM). The presence of a 4-en-3-one grouping in the A-ring of the compounds seems to be indispensable for antiplasmodial activity; progesterone (having the same functional group in the steroid A-ring) has also displayed antiplasmodial activity. Quantitative correlations between molecular structure and bioactivity were thus explored in diosgenone and several derivatives using well-established 3D-QSAR techniques. The models showed that combining electrostatic (70%) and steric (30%) fields can explain most variance regarding compound activity. Malarial parasitemia in mice became reduced by oral administration of two diosgenone derivatives.
- Pabon, Adriana,Escobar, Gustavo,Vargas, Esteban,Cruz, Victor,Notario, Rafael,Blair, Silvia,Echeverri, Fernando
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p. 3356 - 3378
(2013/05/22)
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