Antitumor efficacy and apoptotic activity of substituted chloroalkyl 1H-benz[de]isoquinoline-1,3-diones: a new class of potential antineoplastic agents
IR@IIIM: CSIR-Indian Institute of Integrative Medicine, Jammu
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| Title |
Antitumor efficacy and apoptotic activity of substituted chloroalkyl 1H-benz[de]isoquinoline-1,3-diones: a new class of potential antineoplastic agents
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| Creator |
Mukherjee, Asama
Hazra, Suva Dutta, Sushanta Muthiah, Shanmugavel Mondhe, Dilip Manikrao Sharma, Parduman Raj Singh, Shashank Kumar Saxena, Ajit Kumar Qazi, Gulam Nabi Sanyal, Utpal |
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| Subject |
Chemical Sciences
Pharmacological Sciences |
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| Description |
A series of ten chloroalkyl 1H-benz[de]isoquinoline-1,3-diones (naphthalimides) were synthesized and evaluated for antitumor activity. Amongst them, new compounds 2d and 2i carrying a 6-NO2 substituent in the aromatic portion of the molecule possessed significant antineoplastic activity. The most active compound 2i had elicited significant cytotoxicity in 15 human tumor cell lines namely Leukemia: MOLT-4, HL-60; Lymphoma: U-937; Colon: 502713, HT-29, SW-620,HCT-15, COLO-205; Liver: Hep-2; Prostate DU-145, PC-3;Breast: MCF-7; Neuroblastoma: IMR-32, SK-N-SH and
Ovary: OVCAR-5 out of the 17 cell lines screened. Flow
cytometric analysis performed to study the effect of
compound 2i on the progression of cell cycle of MOLT-4
cells, revealed rise in sub-G1 fraction and concomitant
accumulation of cells in S and G2/M phases, indicating
apoptosis, mitotic arrest and/or delay in exit of daughter cells from mitotic cycle respectively. It also induced caspasemediated apoptosis of MOLT-4 cells in a dose dependant manner. Light and electron microscopic studies revealed characteristic morphology of apoptotic MOLT-4 cells after in vitro treatment with 10 μM concentration of the compound.Apoptosis induction was also observed in HL-60 cells by compounds 2d and 2i to an extent much greater than
camptothecin and cis-platin at 10 μM concentration. Both the
compounds have shown minimal suppressive effect on human
PBMC having high IC50 values of 3,582 and 1,536 μM respectively. These compounds inhibited DNA and RNA synthesis in murine ascites Sarcoma-180 tumor cells in vitro at 8 μM concentration. Above results indicate promising chemotherapeutic potential of the key compound 2i.
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| Date |
2011
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://iiim.csircentral.net/217/1/10.1007s10637%2D009%2D9372%2Dz.pdf
Mukherjee, Asama and Hazra, Suva and Dutta, Sushanta and Muthiah, Shanmugavel and Mondhe, Dilip Manikrao and Sharma, Parduman Raj and Singh, Shashank Kumar and Saxena, Ajit Kumar and Qazi, Gulam Nabi and Sanyal, Utpal (2011) Antitumor efficacy and apoptotic activity of substituted chloroalkyl 1H-benz[de]isoquinoline-1,3-diones: a new class of potential antineoplastic agents. Investigational New Drugs, 29 (3). pp. 434-442. ISSN 0167-6997 |
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| Relation |
http://dx.doi.org/10.1007/s10637-009-9372-z
http://iiim.csircentral.net/217/ |
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