Synthesis and evaluation of new coumarin-pyridine hybrids with promising anti-osteoporotic activities.
Anti-osteoporotic effects of the newly synthesized coumarin-pyridine hybrids were evaluated in primary cultures of rat calvarial osteoblasts in vitro. Compounds 6a, i, j and k were potent in stimulating osteoblast differentiation and mineralization as assessed by the alkaline phosphatase production and alizarin red-S staining assay, respectively. These compounds were also found to be nontoxic in osteoblast cells as compared to the control group in an MTT assay. Furthermore, the effect of these compounds on the transcript levels of osteogenic genes revealed that the compound 6j robustly enhanced mineralization of the osteogenic genes in calvarial osteoblasts. In this context, compound 6j was selected as a potential lead for further structural optimization in the development of new anti-osteoporotic agents.
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, P.O. Box 173, Lucknow 226031, India. Electronic address: sashidhar123@gmail.com.
Koneni V
KV
Sashidhara
Ram K
RK
Modukuri
Dharmendra
D
Choudhary
K
K
Bhaskara Rao
Manoj
M
Kumar
Vikram
V
Khedgikar
Ritu
R
Trivedi
D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D050071:Bone Density Conservation Agents; D003374:Coumarins; D011725:Pyridines; C030123:coumarin; C023666:pyridine
Coumarin; Hybrid; Osteoporosis; Pyridine; Synthesis