Synthesis, Characterization Of Chiral Ruthenium (Ⅱ) Complexes With Alkynes As Apoptosis Inducers

Chiral ruthenium(Ⅱ) complexes have long been investigated as potentialinhibitor in chemotherapy, and numbers of evidences shown that chiral ruthenium(Ⅱ)complexes with enlarged aromatic main ligand can bind to DNA molecules inintercalating, groove binding and electrostatic binding mode, and some entity withhigh antitumor activity have been reported. Recently research shown thatruthenium(Ⅱ) complexes can exert their toxicity through a mitochondria relayedpathway rather than the nuclear DNA mode of action similar to cisplatin. Chen andco-worker demonstrated that chiral ruthenium(Ⅱ) complexes coordinated by tFMPIP(tFMPIP=2-(trifluoromethyphenyl)-1H-imidazo[4,5f][1,10] phenanthroline) caninduce apoptosis of tumor cells through caspase signal pathway by regulating theexpression of Bcl-2family protein. Nevertheless, little candidates with excellentinhibitor activity was reported to enter into clinic ascribe to the high hypdrophobicof chiral ruthenium(Ⅱ) complexes to prohibit the candidate cross the membrane oftumor cells, never to nuclei membrane with poor cellular uptake. Recently, theappended π-conjugated systems, such as alkynes, which offered advantageousbinding properties with respect to the corresponding biological targets via thestronger interactions afforded by a larger aromatic binding surface, have beenattracted more and more attention in drug design. In this paper, a series of chiralruthenium(Ⅱ) complex with alkynes have been synthesized by using Sonogashiracoupling reaction under irradiation of microwave. It’s confirmed firstly that theexisting of alkyne group can make chiral ruthenium(Ⅱ) enter into the MDA-MB-231 cells efficiently. The further studies shown that this type of chiral ruthenium(Ⅱ)complexes can act as potential apoptosis inducers of tumor cells by binding andregulating the expression of miR-21. It’s firstly confirmed that miR-21could berecognized and stabilized by chiral ruthenium(Ⅱ) complexes with alkynes, and45.8%of miR-21gene expression (mean expression of positive control=100) inhuman breast cancer cells (MDA-MB-231cells) were smothered after treatment withthe target compounds.In conclusion, a series of novel chiral ruthenium(Ⅱ) complexes with alkyneshave been designed and synthesized by Sonogahsira coupling reaction undermicro-assisted. It’s found that the target complexes could enter the cells efficientlyand rapidly, and mostly distribute in nucleus of breast cancer cells (MDA-MB-231).The further studies shown that this type of chiral ruthenium(Ⅱ) complexes candistribute in nucleus of cancer cells, and induce apoptosis of MDA-MB-231breastcancer cells by regulating the expressing of miR-21.