2. Academic Validation
  3. Synthesis of enamino-2-oxindoles via conjugate addition between α-azido ketones and 3-alkenyl oxindoles: Cytotoxicity evaluation and apoptosis inducing studies

Synthesis of enamino-2-oxindoles via conjugate addition between α-azido ketones and 3-alkenyl oxindoles: Cytotoxicity evaluation and apoptosis inducing studies

  • Bioorg Med Chem Lett. 2018 Dec 1;28(22):3564-3573. doi: 10.1016/j.bmcl.2018.07.038.
Niggula Praveen Kumar 1,  Yogesh Vanjari 1,  Sowjanya Thatikonda 2,  Venkatesh Pooladanda 2,  Pankaj Sharma 1,  Balasubramanian Sridhar 3,  Chandraiah Godugu 4,  Ahmed Kamal 5,  Nagula Shankaraiah 6
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 2 Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 3 Laboratory of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 4 Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: chandra.niperhyd@gov.in.
  • 5 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India; School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110062, India. Electronic address: ahmedkamal@iict.res.in.
  • 6 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.
PMID: 30318440 DOI: 10.1016/j.bmcl.2018.07.038
Abstract

A facile method for the construction of double bond between 3-ylidene oxindoles and α-azido ketones has been successfully accomplished with a mild base. This method features azido reduction with concomitant double bond formation to provide the new class of bioactive enamino-2-oxindoles. These new compounds were screened for their in vitro cytotoxic potential on selected human Cancer cell lines such as colon, lung, breast, and cervical Cancer cells. Among them, representative compounds 3a, 3h, 3k, 3p, 3w and 3x showed notable cytotoxicity profile with IC50 values ranging from 1.40 ± 0.10 to 28.7 ± 0.36 µM. Compound 3k displayed most potent cytotoxicity against lung Cancer (NCI-H460) cells with an IC50 value of 1.40 ± 0.10 µM. 3k also arrested the G2/M phase of the cell cycle and induced distinctive apoptotic features on lung Cancer cells. The Apoptosis induction is supported by various cellular assays such as AO/EB, DAPI, and DCFDA staining studies including clonogenic assay. Extent of Apoptosis was also analyzed by Annexin binding and JC-1 staining. Moreover, this method is amenable for the generation of a library of new class of stable bioactive enamino-2-oxindoles.

Keywords

Apoptosis; Azido reduction; CC bond formation; Conjugate addition; Cytotoxicity; Enamino-2-oxindoles.

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