Tags

Type your tag names separated by a space and hit enter

Antiproliferative activity of chalcones with basic functionalities.
Bioorg Med Chem. 2007 Nov 15; 15(22):7021-34.BM

Abstract

A library of chalcones with different basic groups were synthesized and evaluated for antiproliferative activities against the human breast cancer (MCF 7) and colon cancer (HCT 116) cell lines. Structure-activity relationships were analyzed by projection methods (PCA/PLS) and multiple linear regression. Polar volume, hydrogen bonding features, HOMO energies, and charge on the beta carbon were found to be important factors. A basic group on either ring A or B of the chalcone led to a favourable increase in polar volume, but when present on ring B, it increased HOMO energies and decreased the positive charge on the beta carbon, both of which led to lower activity. Several examples showed that final activity of the chalcone was influenced by compensatory interactions among these parameters. In general, a single basic group on ring A was associated with good activity. A notable exception was compound 1-123 which had basic groups on both rings A and B but still maintained a good activity profile with IC(50)<10 microM and selectivity ratios >2.5. There was some evidence to show that structural differences in chalcones influenced not only activity but mechanism of action. Compounds 6-130 and 7-140 which had basic groups on ring A interfered with cell cycle progression, but the dibasic chalcone 1-123 had no effect.

Authors+Show Affiliations

Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17804245

Citation

Liu, Xiaoling, and Mei-Lin Go. "Antiproliferative Activity of Chalcones With Basic Functionalities." Bioorganic & Medicinal Chemistry, vol. 15, no. 22, 2007, pp. 7021-34.
Liu X, Go ML. Antiproliferative activity of chalcones with basic functionalities. Bioorg Med Chem. 2007;15(22):7021-34.
Liu, X., & Go, M. L. (2007). Antiproliferative activity of chalcones with basic functionalities. Bioorganic & Medicinal Chemistry, 15(22), 7021-34.
Liu X, Go ML. Antiproliferative Activity of Chalcones With Basic Functionalities. Bioorg Med Chem. 2007 Nov 15;15(22):7021-34. PubMed PMID: 17804245.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiproliferative activity of chalcones with basic functionalities. AU - Liu,Xiaoling, AU - Go,Mei-Lin, Y1 - 2007/08/21/ PY - 2007/05/30/received PY - 2007/07/18/revised PY - 2007/07/20/accepted PY - 2007/9/7/pubmed PY - 2008/1/25/medline PY - 2007/9/7/entrez SP - 7021 EP - 34 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 15 IS - 22 N2 - A library of chalcones with different basic groups were synthesized and evaluated for antiproliferative activities against the human breast cancer (MCF 7) and colon cancer (HCT 116) cell lines. Structure-activity relationships were analyzed by projection methods (PCA/PLS) and multiple linear regression. Polar volume, hydrogen bonding features, HOMO energies, and charge on the beta carbon were found to be important factors. A basic group on either ring A or B of the chalcone led to a favourable increase in polar volume, but when present on ring B, it increased HOMO energies and decreased the positive charge on the beta carbon, both of which led to lower activity. Several examples showed that final activity of the chalcone was influenced by compensatory interactions among these parameters. In general, a single basic group on ring A was associated with good activity. A notable exception was compound 1-123 which had basic groups on both rings A and B but still maintained a good activity profile with IC(50)<10 microM and selectivity ratios >2.5. There was some evidence to show that structural differences in chalcones influenced not only activity but mechanism of action. Compounds 6-130 and 7-140 which had basic groups on ring A interfered with cell cycle progression, but the dibasic chalcone 1-123 had no effect. SN - 0968-0896 UR - https://www.unboundmedicine.com/medline/citation/17804245/Antiproliferative_activity_of_chalcones_with_basic_functionalities_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(07)00659-1 DB - PRIME DP - Unbound Medicine ER -