- Design, synthesis, and biological evaluation of new series of pyrrol-2(3H)-one and pyridazin-3(2H)-one derivatives as tubulin polymerization inhibitors
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A potential microtubule destabilizing series of new thirty-five Pyrrol-2-one, Pyridazin-3(2H)-one and Pyridazin-3(2H)-one/oxime derivatives has been synthesized and tested for their antiproliferative activity against a panel of 60 human cancer cell lines. Compounds IVc, IVg and IVf showed a broad spectrum of growth inhibitory activity against cancer cell lines representing renal, cancer of lung, colon, central nervous system, ovary, and kidney. Among them, compound IVg was found to have broad spectrum anti-tumor activity against the tested nine tumor subpanels with selectivity ratios ranging between 0.21 and 3.77 at the GI50 level. In vitro assaying revealed tubulin polymerization inhibition by all active compounds IVc, IVg and IVf. The results of the docking study revealed nice fitting of compounds IVc, IVf, and IVg into CA-4 binding site in tubulin. The three compounds exhibited high binding affinities (ΔGb = ?12.49 to ?12.99 kcal/mol) toward tubulin compared to CA-4 (?8.87 kcal/mol). Investigation of the binding modes of the three compounds IVc, IVf, and IVg revealed that they interacted mainly hydrophobically with tubulin and similar binding orientations to that of CA-4. These observations suggest that tubulin is a possible target for these compounds.
- Abdelbaset, Mahmoud S.,Abdelrahman, Mostafa H.,Bukhari, Syed Nasir Abbas,Gouda, Ahmed M.,Youssif, Bahaa G.M.,Abdel-Aziz, Mohamed,Abuo-Rahma, Gamal El-Din A.
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- Synthesis of multi-functional alkenes via Wittig reaction with a new-type of phosphorus ylides
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A Bu3P-mediated mild and efficient synthesis of multi-functional alkenes has been described starting from substituted acrylate with aldehydes. In situ generated zwitterionic intermediates underwent proton-exchange to afford ylide intermediates, which were trapped by corresponding aldehydes providing the products in up to 92% yield with complete E-stereoselectivity. Further derivatization of the products was performed to furnish functional pyridazinones.
- Tsai, Yi-Ling,Syu, Siang-En,Yang, Shu-Mei,Das, Utpal,Fan, Yu-Shiou,Lee, Chia-Jui,Lin, Wenwei
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p. 5038 - 5045
(2014/12/10)
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- Synthesis of multi-functional alkenes via Wittig reaction with a new-type of phosphorus ylides
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A Bu3P-mediated mild and efficient synthesis of multi-functional alkenes has been described starting from substituted acrylate with aldehydes. In situ generated zwitterionic intermediates underwent proton-exchange to afford ylide intermediates, which were trapped by corresponding aldehydes providing the products in up to 92% yield with complete E-stereoselectivity. Further derivatization of the products was performed to furnish functional pyridazinones.
- Tsai, Yi-Ling,Syu, Siang-En,Yang, Shu-Mei,Das, Utpal,Fan, Yu-Shiou,Lee, Chia-Jui,Lin, Wenwei
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p. 5038 - 5045
(2014/07/08)
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- Conversion of α-Arylidene-γ-phenyl-Δβ,γ-butenolides into Nitrogen Heterocycles
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Treatment of α-arylidene-γ-phenyl-Δβ,γ-butenolides (I) with strong nucleophiles brings about opening of the γ-lactone ring with the formation of acyclic acid derivatives (II).The acid hydrazides (IIa-d) undergo facile condensation with carbonyl
- Khattab, Samir A.,Hosny, Mohammad M.
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p. 1038 - 1043
(2007/10/02)
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