Mahanine, A DNA Minor Groove Binding Agent Exerts Cellular Cytotoxicity with Involvement of C‑7-OH and −NH Functional Groups
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Mahanine, A DNA Minor Groove Binding Agent Exerts Cellular
Cytotoxicity with Involvement of C‑7-OH and −NH Functional
Groups
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| Creator |
Samanta, Suman K.
Dutta, Devawati Roy, Sarita Bhattacharya, Kaushik Sarkar, Sayantani Dasgupta, Anjan K. Pal, Bikas C. Mandal, Chhabinath Mandal, Chitra |
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| Subject |
Cancer Biology and Inflammatory Disorder Division
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| Description |
Mahanine, a carbazole alkaloid is a potent anticancer molecule. To recognize the structure−activity correlation, mahanine was chemically modified. Antiproliferative activity of these derivatives was determined in 19 cancer cell line from seven different origins. Mahanine showed enhanced apoptosis compared to dehydroxy-mahanine-treated cells, indicating significant contribution of the C-7-OH group. O-Methylated-mahanine and N-methylated dehydroxy-mahanine-treated cells exhibited apoptosis only at higher concentrations, suggesting additional contribution of 9-NH group. Using biophysical techniques, we demonstrated that mahanine interacts with DNA through strong association with phosphate backbone compared to otherderivatives but is unable to induce any conformational change in DNA, hence suggestingthe possibility of being a minor groove binder. This was corroborated by molecular modeling and isothermal titration calorimetry studies. Taken together, the results of the current study represent the first evidence of involvement of C-7-OH and 9-NH group of mahanine for its cytotoxicity and its minor groove binding ability with DNA
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| Publisher |
American Chemical Society
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| Date |
2013
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1987/1/Journal_of_Medicinal_Chemistry_2013.pdf
Samanta, Suman K. and Dutta, Devawati and Roy, Sarita and Bhattacharya, Kaushik and Sarkar, Sayantani and Dasgupta, Anjan K. and Pal, Bikas C. and Mandal, Chhabinath and Mandal, Chitra (2013) Mahanine, A DNA Minor Groove Binding Agent Exerts Cellular Cytotoxicity with Involvement of C‑7-OH and −NH Functional Groups. Journal of Medicinal Chemistry. |
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| Relation |
http://dx.doi.org/10.1021/jm400290q
http://www.eprints.iicb.res.in/1987/ |
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