2. Academic Validation
  3. Synthesis and biological evaluation of spiro[cyclopropane-1,3'-indolin]-2'-ones as potential anticancer agents

Synthesis and biological evaluation of spiro[cyclopropane-1,3'-indolin]-2'-ones as potential anticancer agents

  • Bioorg Med Chem Lett. 2015 Oct 15;25(20):4580-6. doi: 10.1016/j.bmcl.2015.08.056.
Chada Narsimha Reddy 1,  V Lakshma Nayak 1,  Geeta Sai Mani 2,  Jeevak Sopanrao Kapure 2,  Praveen Reddy Adiyala 1,  Ram Awatar Maurya 3,  Ahmed Kamal 4
Affiliations

Affiliations

  • 1 Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
  • 2 Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Hyderabad 500 007, India.
  • 3 Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India. Electronic address: ramaurya@iict.res.in.
  • 4 Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India; Chemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Hyderabad 500 007, India. Electronic address: ahmedkamal@iict.res.in.
PMID: 26330077 DOI: 10.1016/j.bmcl.2015.08.056
Abstract

Libraries of spiro[cyclopropane-1,3'-indolin]-2'-ones were synthesized and evaluated for their biological activity against five different human Cancer cell lines HT-29 (colon Cancer), DU-145 (prostate Cancer), Hela (cervical Cancer), A-549 (Lung Cancer), and MCF-7 (breast Cancer). Many compounds of the series exhibited promising Anticancer activity (IC50<20 μM) against the studied cell lines. Based on the screening results, a structure activity relationship (SAR) of the pharmacophore was proposed. Among the series compound 6b and 6u showed significant activity against human prostate Cancer cell line, DU-145. Flow cytometric analysis showed that these two compounds arrested the cell cycle in the G0/G1 phase leading to Caspase-3 dependent apoptotic cell death. Further, measurement of mitochondrial membrane potential and Annexin V-FITC assay also suggested that 6b and 6u induced cell death by Apoptosis.

Keywords

Anticancer agents; Cyclopropane; Spirooxindoles; Structure–activity relationship (SAR).

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