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

Medicinal Chemistry Research volume 22, pages 5901–5911 (2013)Cite this article

Abstract

A series of novel substituted aminobenzophenone derivatives containing nitrogen mustard moiety (5a–f) were synthesized and characterized on the basis of their IR, 1H NMR, 13C 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).

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Acknowledgments

Authors are thankful to College Managing Committee, SCOP, Nangal for providing necessary facilities to carry out research work. Authors wish to express their gratitude to Dr. Manoj Kumar, Professor of Pharmaceutical Chemistry, UIPS, Panjab University, Chandigarh to carry out ADME study at his lab. Authors are also thankful to ISFAL, ISF College of Pharmacy, Moga (Punjab) for carrying out cell line studies and SAIF, Panjab University, Chandigarh for cooperation in getting the spectral data.

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Authors and Affiliations

  1. Pharmaceutical Chemistry Division, Shivalik College of Pharmacy, Nangal, Rupnagar, 140126, Punjab, India

    Rajesh K. Singh & D. N. Prasad

  2. Indo-Soviet Friendship (ISF) College of Pharmacy, Moga, 142001, Punjab, India

    T. R. Bhardwaj

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  1. Rajesh K. Singh
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  2. D. N. Prasad
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  3. T. R. Bhardwaj
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Correspondence to Rajesh K. Singh.

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

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Singh, R.K., Prasad, D.N. & Bhardwaj, T.R. Design, synthesis and evaluation of aminobenzophenone derivatives containing nitrogen mustard moiety as potential central nervous system antitumor agent. Med Chem Res 22, 5901–5911 (2013). https://doi.org/10.1007/s00044-013-0582-8

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  • DOI: https://doi.org/10.1007/s00044-013-0582-8

Keywords

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