Molecular docking and synthesis of caffeic acid analogous and its anti-inflammatory, analgesic and ulcerogenic studies.

A series of caffeic acid (CA) derivatives 7a-j were synthesized via etherification and coupling action and their chemical structures were elucidated spectroscopically. Motivated by the various biological activities displayed by CA derivatives such as anti-inflammatory, antiviral, anticancer and antioxidant and also based on its extensively consumption in the human diet. In the present work, the newly synthesized compounds 7a-j were evaluated for anti-inflammatory and analgesic action and most of them exerted comparable activity to the reference compound celecoxib. Further, ulcer indexes for the most active compounds were calculated and most of them showed less ulcerogenic effect than the reference drug. Among the title series 7a-j, compounds 7f and 7g with electron withdrawing bromo and chloro group respectively, at the para position of the phenoxy ring was showed good activity compared to all other compounds. Interestingly, the COX-I/COX-II activity ratio of potent compounds 7f and7g showed an almost equal inhibitory effect on both isoenzymes. Further, molecular docking studies have been performed for the potent compounds which showed statistically significant result.

Correction: The critical role of novel benzophenone analogs on tumor growth inhibition targeting angiogenesis and apoptosis.

[This corrects the article DOI: 10.1039/C7MD00593H.].

The critical role of novel benzophenone analogs on tumor growth inhibition targeting angiogenesis and apoptosis.

In modern biology, one of the major topics of importance is progress in anti-cancer drugs with specific targets. The angiopreventive and in vitro tumor inhibition activities of novel synthetic benzophenone analogs have been investigated intensively and explored in a very systematic way. Novel benzophenone analogs (9a-d and 10a-d) substituted with methyl, chloro and fluoro groups at different positions on an identical chemical backbone and incorporating variations in the number of substituents have been synthesized in a multistep process and characterized. In this study, we further evaluate the newly synthesized compounds for their cytotoxic and anti-proliferative effects against A549, HeLa and MCF-7 cells. The potent lead compound was further assessed for anti-angiogenic effects. Through the structure-activity relationship, we found that an increase in the number of methyl, chloro and fluoro groups in a benzophenone ring on compound 9d resulted in higher potency compared to other compounds. Tumor inhibition was notably promoted, and this was reflected in effects on neovessel formation in in vivo systems, such as the CAM. Compound 9d interacts with rVEGF through hydrogen bonds in silico, thereby down-regulating the expression of VEGF in angiogenesis. From our investigation, it is suggested on the basis of clonogenesis and cell migration assays that compound 9d has the potency to exhibit prolonged activity against cancer progression, through cell cycle arrest at the G2/M phase. In addition, compound 9d inhibits A549 cells through caspase-activated DNase-mediated apoptosis.