Neo-tanshinlactone inspired synthesis, in vitro evaluation of novel substituted benzocoumarin derivatives as potent anti-breast cancer agents.
A small library of novel benzocoumarin derivatives based on naturally occurring neo-tanshinlactone scaffold was constructed and their antiproliferative activities against breast cancer cells MCF-7 and MDA-MB-231 were evaluated. A number of derivatives showed good anti-breast cancer activity, in some cases higher to that of the reference compound tamoxifen. In particular, benzocoumarins Bc-5, Bc-8 and Bc-9 strongly inhibited the proliferation of MCF-7 cancer cell line with the IC(50) values of 3.8, 7.9 and 6.5 μM, respectively. The compounds were capable of inducing nuclear fragmentation, cell cycle arrest and caspase dependent apoptosis in MCF-7 cell lines. In addition, these derivatives were devoid of cytotoxic effect against normal osteoblast cells. These synthetic benzocoumarins hold promises for developing safer alternative to the existing anti-breast cancer agents.
Medicinal and Process Chemistry Division, Central Drug Research Institute, CDRI-CSIR, Lucknow, India. kv_sashidhara@cdri.res.in
Koneni V
KV
Sashidhara
Jammikuntla N
JN
Rosaiah
Manoj
M
Kumar
Rishi Kumar
RK
Gara
Lakshma Vadithe
LV
Nayak
Kamini
K
Srivastava
Hemant Kumar
HK
Bid
Rituraj
R
Konwar
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D005663:Furans / Q000737:chemistry*; D006801:Humans; D011753:Pyrones / Q000737:chemistry*; D054852:Small Molecule Libraries
D000970:Antineoplastic Agents; D003374:Coumarins; D005663:Furans; D011753:Pyrones; D054852:Small Molecule Libraries; C494351:neotanshinlactone