Synthesis and biological evaluation of spiro[cyclopropane-1,3'-indolin]-2'-ones as potential anticancer agents.
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.
Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Chada Narsimha
CN
Reddy
Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
V Lakshma
VL
Nayak
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.
Geeta Sai
GS
Mani
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.
Jeevak Sopanrao
JS
Kapure
Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Praveen Reddy
PR
Adiyala
Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India. Electronic address: ramaurya@iict.res.in.
Ram Awatar
RA
Maurya
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.
Ahmed
A
Kamal
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D003521:Cyclopropanes; D007211:Indoles; C000608298:spiro(cyclopropane-1,3'-indolin)-2'-one
Anticancer agents; Cyclopropane; Spirooxindoles; Structure–activity relationship (SAR)