Chinese Journal of Applied Chemistry ›› 2018, Vol. 35 ›› Issue (11): 1317-1324.DOI: 10.11944/j.issn.1000-0518.2018.11.170398

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Synthesis, Crystal Strutures and Phototoxicity in Vitro of Nitrogen Mustard-Linked Bis(arylmethylidene)cycloalkanones

QU Xiaofang,CAO Yaping,WU Qing,HU Qinghong,YUAN Zeli()   

  1. School of Pharmacy,Zunyi Medical University,Zunyi,Guizhou 563003,China
  • Received:2017-11-07 Accepted:2018-02-05 Published:2018-10-31 Online:2018-10-31
  • Contact: YUAN Zeli
  • Supported by:
    Supported by the National Natural Science Foundation of China(No.81360471, No.81660575), Guizhou Province International Cooperation(No.[2012]7036), Health Committee Funded Projects(No.gzwjkj-2015-01-001), the Ministry of Education Chunhui Program Funded Projects(No.Z2016004)

Abstract:

In order to build photodynamic therapy and chemotherapy synergy anticancer leading compounds, three novel nitrogen mustard-linked bis(arylmethylidene)cycloalkanone compounds 3a~3c and other three bis(arylmethylidene)-cycloalkanone compounds 3d~3f were designed and synthesized based on principle of efficacy hybridization. Their structures were characterized by nuclear magnetic resonance spectroscopy(NMR), high resolution mass spectrometry(ESI-MS), X-ray diffraction(XRD) and Fourier transform infrared spectrometer(FTIR). Their in vitro phototoxicity were investigated by thiazolyl blue tetrazolium bromide(MTT) method against A549(human lung adenocarcinoma) and HepG2(human hepatoma) cell lines. The preliminary data indicates that most of these compounds exhibit moderate to potent phototoxicity against both tumor cell lines. In particular, compound 3a is worthy of further study with an IC50 of against HepG2 at 2.0 nmol/mL. Compounds 3a and 3d were simulated at B3LYP 6-311G+ level with Gaussian09 program. Their optimized geometries and the energy of frontier molecular orbitals are obtained. Furthermore, the relationship between the structural features and phototoxicity were analyzed based on the energy of frontier molecular orbitals.

Key words: bis(arylmethylidene)cycloalkanone, crystal strutures, phototoxicity