Design and synthesis of 3-arylbenzopyran based non-steroidal vitamin-D3 mimics as osteogenic agents

3-Arylbenzopyran based non-steroidal osteogenic agents have been explored as structural templates of estrogen and vitamin-D-3. The target molecules 18a-c, 19a-c, 26a-c, 27a-c and intermediates 17a-c and 25a-c were studied for their osteogenic activity in an osteoblast differentiation assay in vitro using mouse calvarial osteoblast cells. Compounds 25c, 26b, 27b and 27c effectively increased ALP activity at 1 pM concentration compared to the untreated cells. The active compounds were devoid of inherent toxicity at 1 pM concentration in osteoblast cells. The most active compound, 27b, was studied for mineralization of osteoblast cells and expression of marker genes, viz. BMP-2, RUNX-2 & Osx, involved in osteogenesis. Molecular docking analysis performed for 27b showed its possible interactions with estrogen receptor-a and -beta (ER-alpha and ER-beta) as well as the vitamin-D receptor (VDR).