Curcumin, a popular herbal medicine derived from turmeric, blocks the synthesis of prostaglandins by inhibiting Cyclooxygenase-1 and 2 (COX-1 and COX2). We have recently reported an efficient method of synthesizing curcumin and synthesised analogues. In the present study, we have investigated sixteen novel analogues of curcumin for their ability to inhibit COX-1 and COX-2. We report here that most of the curcumin analogues display selective inhibition of COX-2, whereas a few suppress COX-1 activity. Further, we examined the binding of these inhibitors by molecular docking and observed that the compound with pronounced selectivity for COX-2 displayed better binding to COX-2 compared to curcumin. © 2021 Elsevier B.V.