Design, synthesis and evaluation of aminobenzophenone derivatives containing nitrogen mustard moiety as potential central nervous system antitumor agent

作者：Singh Rajesh K^*; Prasad D N; Bhardwaj T R

来源：Medicinal Chemistry Research, 2013, 22(12): 5901-5911.

DOI：10.1007/s00044-013-0582-8

• 2-Aminobenzophenone
• Nitrogen mustard
• Blood-brain barrier
• Physicochemical ADME descriptors
• NBP assay
• In vitro cytotoxicity

A series of novel substituted aminobenzophenone derivatives containing nitrogen mustard moiety (5a-f) were synthesized and characterized on the basis of their IR, H-1 NMR, C-13 NMR, CHN, and mass spectral data. All the compounds when evaluated for chemical 4-(4-nitrobenzyl) pyridine alkylating activity proved to be active alkylating agents. All the synthesized compounds were subjected to physicochemical parameters determination required for central nervous system (CNS) activity through computational, online software, and QikProp 3.2. The log P values and other in silico ADME physicochemical descriptors analyzed lay between the ranges those are required for good BBB penetration. The in vitro antiproliferative activity against human cancer cell lines viz. A 549 (lung), COLO 205 (colon), U 87 (glioblastoma), and IMR-32 (neuroblastoma) was investigated. Most of the test compounds showed potent antitumor activity, especially compound (5f) which displayed the highest activity against CNS cancer cell line comparable to that of chlorambucil and docetaxel. The preliminary structure-activity relationship (SAR) revealed that 5-chloroaminobenzophenone-mustard series (5a-c) exhibited better antitumor activity than 5-nitroaminobenzophenone-mustard series (5d-f).

• 出版日期2013-12