Please use this identifier to cite or link to this item: http://dspace.library.iitb.ac.in/xmlui/handle/123456789/18970
Title: Dihydrochelerythrine and its derivatives: Synthesis and their application as potential G-quadruplex DNA stabilizing agents
Authors: MALHOTRA, R
RARHI, C
DIVESHKUMAR, KV
BARIK, R
D'CUNHA, R
DHAR, P
KUNDU, M
CHATTOPADHYAY, S
ROY, S
BASU, S
PRADEEPKUMAR, PI
HAJRA, S
Keywords: Benzophenanthridine Alkaloids
Circular-Dichroism
Small-Molecule
Chelerythrine
6-Acetonyldihydrochelerythrine
Sanguinarine
Aggregation
Cyclization
Nitidine
Promoter
Issue Date: 2016
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
Citation: BIOORGANIC & MEDICINAL CHEMISTRY,24(13)2887-2896
Abstract: A convenient route was envisaged toward the synthesis of dihydrochelerythrine (DHCHL), 4 by intramolecular Suzuki coupling of 2-bromo-N-(2-bromobenzyl)-naphthalen-1-amine derivative 5 via in situ generated arylborane. This compound was converted to (+/-)-6-acetonyldihydrochelerythrine (ADC), 3 which was then resolved by chiral prep-HPLC. Efficiency of DHCHL for the stabilization of promoter quadruplex DNA structures and a comparison study with the parent natural alkaloid chelerythrine (CHL), 1 was performed. A thorough investigation was carried out to assess the quadruplex binding affinity by using various biophysical and biochemical studies and the binding mode was explained by using molecular modeling and dynamics studies. Results clearly indicate that DHCHL is a strong G-quadruplex stabilizer with affinity similar to that of the parent alkaloid CHL. Compounds ADC and DHCHL were also screened against different human cancer cell lines. Among the cancer cells, (+/-)-ADC and its enantiomers showed varied (15-48%) inhibition against human colorectal cell line HCT116 and breast cancer cell line MDA-MB-231 albeit low enantio-specificity in the inhibitory effect; whereas DHCHL showed 30% inhibition against A431 cell line only, suggesting the compounds are indeed cancer tissue specific. (C) 2016 Elsevier Ltd. All rights reserved.
URI: http://dx.doi.org/10.1016/j.bmc.2016.04.059
http://localhost:8080/xmlui/handle/123456789/18970
ISSN: 0968-0896
1464-3391
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