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Synthesis and Bioevaluation of Quaternary Centered 3-hydroxy-3 (alkynyl)indolin-2-one Derivatives as Potential Cytotoxic Agents and Akt Kinase Inhibitors

[ Vol. 17 , Issue. 14 ]

Author(s):

P. Sai Prathima*, R. Bikshapathi , Y. Poornachandra , V. Himabindu, G. Jagadeesh Kumar, N. Jagadeesh, C. Ganesh Kumar and V. Jayathirtha Rao*   Pages 1963 - 1970 ( 8 )

Abstract:


Abstract: Background: Alkynes are fundamental building blocks in synthetic chemistry with high pharmaceutical applications. Among the bioactive acetylenic molecules, propargylic alcohol is most important as almost all the marketed drugs contains quaternary centered propargylic alcohol functionality.

Objective: In this study we have synthesised and evaluated 3-hydroxy-3-ethynylindolin-2-one derivatives for in vitro cytotoxic activity.

Method: An expeditious method for direct alkynylation of isatins (ketones) has been developed using tetrabutylammonium fluoride (TBAF) as a catalyst in THF solvent at room temperature under metal-free conditions. Furthermore, this method is an economically viable process that also compliments green aspects like being a ligand/metal free process under ambient conditions. This reaction tolerated a wide range of substrates with good to excellent yields (80-94%).

Results: The results showed that the synthesized compounds (4m, 4n and 4p) has the ability to inhibit Akt kinase activity with IC50 values ranging from 7.7 to 9.8 µM.

Conclusion: All the 3-hydroxy-3-ethynylindolin-2-one derivatives were subjected for in vitro cytotoxic activity on five different cancer cell lines. Further, the synthesized compounds (4m, 4n and 4p) were evaluated for their ability to inhibit Akt kinase activity and exhibited good inhibition with IC50 values ranging from 7.7 to 9.8 µM..

Keywords:

Alkynylation, oxindoles, TBAF, N-substituted isatins, Akt kinase activity, 3-hydroxy-3-ethynylindolin-2-one derivatives.

Affiliation:

Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607, Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607, Medicinal Chemistry and Pharmacology Division, (IICT), Hyderabad, Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607, Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607, X-ray Crystallography Division(IICT), Hyderabad, Medicinal Chemistry and Pharmacology Division, (IICT), Hyderabad, Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607

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