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Mahanine, A DNA Minor Groove Binding Agent Exerts Cellular Cytotoxicity with Involvement of C‑7-OH and −NH Functional Groups

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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
 
Creator Samanta, Suman K.
Dutta, Devawati
Roy, Sarita
Bhattacharya, Kaushik
Sarkar, Sayantani
Dasgupta, Anjan K.
Pal, Bikas C.
Mandal, Chhabinath
Mandal, Chitra
 
Subject Cancer Biology and Inflammatory Disorder Division
 
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
 
Publisher American Chemical Society
 
Date 2013
 
Type Article
PeerReviewed
 
Format application/pdf
 
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.
 
Relation http://dx.doi.org/10.1021/jm400290q
http://www.eprints.iicb.res.in/1987/