Dual targeted 2-Benzylideneindanone pendant hydroxamic acid group exhibits selective HDAC6 inhibition along with tubulin stabilization effect

[Display omitted] •Dual targeted novel anticancer agents on indanone core have been synthesized.•Five analogues exhibited significant antiproliferative activity.•Targets: Dual action; Microtubule destabilization (Antitubulin) and HDAC6 inhibition.•HDAC6 inhibition: 9: high potency-low selectivity while 21: High potency-high selectivity.•Low to moderate anti-inflammatory effect.•9: Safety: in-vivo acute toxicity, rodent model- safe up to 1000 mg/kg dose. Abnormal epigenetics has been recognised as an early event in tumour progression and aberrant acetylation of lysine in particular has been understood in tumorigenesis. Therefore, it has become an attractive target for anticancer drug development. However, HDAC inhibitors have limited success due to toxicity and drug resistance concerns. Present study deals with design and synthesis of bivalent indanone based HDAC6 and antitubulin ligands as anticancer agents. Two of the analogues 9 and 21 exhibited potent antiproliferative activities (IC50, 0.36–3.27 µM) and high potency against HDAC 6 enzyme. Compound 21 showed high selectivity against HDAC 6 while 9 exhibited low selectivity. Both the compounds also showed microtubule stabilization effects and moderate anti-inflammatory effect. Dual targeted anticancer agents with concomitant anti-inflammatory effects will be more attractive clinical candidates in future.