Endo and exo cyclopalladated (E)-N-([1,1'-biphenyl]-2-yl)-1-mesitylmethanimines: Anticancer, antibacterial and antioxidant activities

(E)-N-([1,1'-biphenyl]-2-yl)-1-mesitylmethanimine (imine a) and two structural cyclopalladated isomers of imine a, which contained a six-membered metallacycle and an aliphatic and an aromatic metallated carbon of formula [Pd{CH2-3,5-Me2-6-(CH=N-C6H4-2′-C6H5)C6H2}Br(PPh3)] (3a-endo) and [Pd(C6H4-2-C6H4-2′-N=CH-2,4,6-C6H2Me3)Br(PPh3)] (3a-exo), were synthetized by condensation reaction (imine a) and subsequent cyclometallation, metathesis and splitting reactions (compounds 3a-endo and 3a-exo). Imine a was characterized by high resolution ESI-(+) mass spectrometry, IR, and 1H-NMR, and compounds 3a by elemental analysis, high resolution ESI-(+) mass spectrometry, IR, and 1H- and 31P{1H}-NMR. The structural isomer 3a-exo consisted of a mixture of Z and E geometrical isomers in relation to its carbon-nitrogen double bond. In vitro anticancer, antibacterial and antioxidant activities of structural isomers 3a were compared with those of imine a and those of the six membered cyclopalladated primary amine 3b of formula [Pd(C6H4-2-C6H4-2′-NH2)Br(PPh3)]. Compound 3b was prepared as reported. Compounds 3 cytotoxicity towards cancer and normal cells was very dependent on their structure. Compounds 3a-exo and 3b were more cytotoxic than imine a towards the assayed cancer cell lines. Interestingly, compound 3a-exo with an exo imine function to the palladacycle presented a cytotoxicity in the low micromolar range (5–20 μM) towards the assayed cancer cell lines and was at least seven times less cytotoxic than cisplatin against normal BJ human fibroblast cells. Compounds 3 and imine a presented a noticeable antibacterial and antioxidant activity. Notably, imine a produced an antioxidant activity similar to that of ascorbic acid. Finally, compounds 3 were not efficient for altering the DNA tertiary structure or as inhibitors of cathepsin B.