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Medicinal Chemistry Research

, Volume 25, Issue 2, pp 283–291 | Cite as

Novel 2-(1-(substitutedbenzyl)-1H-tetrazol-5-yl)-3-phenylacrylonitrile derivatives: synthesis, in vitro antitumor activity and computational studies

  • Suresh Maddila
  • Kovashnee Naicker
  • Mehbub I. K. Momin
  • Surjyakanta Rana
  • Sridevi Gorle
  • Suryanarayana Maddila
  • Kotaiah Yalagala
  • Moganavelli Singh
  • Neil A. Koorbanally
  • Sreekantha B. JonnalagaddaEmail author
Original Research

Abstract

This work describes the two-step synthesis of new series of 2-(1-(substitutedbenzyl)-1H-tetrazol-5-yl)-3-phenylacrylonitrile derivatives (6a–k) starting from substituted benzyl halides (5a–k) and 3-phenyl-2-(1H-tetrazol-5-yl)acrylonitrile (4). Initially, compound 4 was synthesized using benzaldehyde, malononitrile and sodium azide. All the synthesized compounds were obtained in good yields and were characterized using 1H NMR, 13C NMR, FTIR and HRMS spectral data. The new compounds (6a–k) were evaluated for their potential in vitro antitumor activity against four human cancer cell lines (MCF-7, CaCO2, HeLa and SkBr3) by MTT assay. The most potent compounds 6b, 6h and 6j show good activity (IC50 values) relative to 5-fluorouracil, with potential to be antitumor agents. Compounds 6a, 6c, 6g, 6f and 6k showed moderate activity. The best performing three compounds (6b, 6h and 6j) were evaluated for in silico analysis on the PharmMapper web server, and the human mitogen-activated protein kinase 1 (MEK-1) enzyme was recognized as the main target protein. MEK-1 inhibition by these compounds was further confirmed by the docking study to corroborate the target.

Graphical Abstract

Keywords

Synthesis Tetrazoles Antitumor activity MEK-1 inhibition 

Notes

Acknowledgments

The authors thank National Research Foundation and University of KwaZulu-Natal, South Africa, for financial assistance and research facilities.

Supplementary material

44_2015_1482_MOESM1_ESM.doc (2 mb)
Supplementary material 1 (DOC 2080 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Suresh Maddila
    • 1
  • Kovashnee Naicker
    • 2
  • Mehbub I. K. Momin
    • 1
  • Surjyakanta Rana
    • 1
  • Sridevi Gorle
    • 2
  • Suryanarayana Maddila
    • 1
  • Kotaiah Yalagala
    • 1
  • Moganavelli Singh
    • 2
  • Neil A. Koorbanally
    • 1
  • Sreekantha B. Jonnalagadda
    • 1
    Email author
  1. 1.School of Chemistry and PhysicsUniversity of KwaZulu-NatalDurbanSouth Africa
  2. 2.Non-viral Gene Delivery Laboratory, Discipline of Biochemistry, School of Life SciencesUniversity of KwaZulu-NatalDurbanSouth Africa

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