Novel 2-(1-(substitutedbenzyl)-1H-tetrazol-5-yl)-3-phenylacrylonitrile derivatives- Synthesis, in vitroantitumor activity and computational studies

Suresh Maddila1, Kovashnee Naicker2, Mehbub I.K. Momin1, Surjyakanta Rana1,Sridevi Gorle2, Suryanarayana Maddila1, Kotaiah Yalagala1, Moganavelli Singh2, Neil A. Koorbanally, Sreekantha B Jonnalagadda1*

*School of Chemistry & Physics, University of KwaZulu-Natal, Westville Campus, Chiltern Hills, Durban-4000, South Africa

*Corresponding Author: Prof. Sreekantha B. Jonnalagadda

School of Chemistry & Physics,

University of KwaZulu-Natal,

Durban 4000, South Africa.

Tel.: +27 31 2607325,

Fax: +27 31 2603091

E-mail address:

Contents / Pages
Materials, methods and instruments (S1) / 2
Computational methods(S2) / 2
Spectra’s of substituted tetrazole derivatives / 3-35

Materials, methods and instruments

All chemicals and reagents required for the reaction were of analytical grade and were used without any further purification. Bruker AMX 400 MHz NMR spectrometerwas used to recordthe 1H NMR, 13C NMR and 15N NMR spectral values. High-resolution mass data were obtained using a Bruker micro TOF-Q II ESI instrument operating at ambient temperature.The DMSO−d6 solution was utilized for this while TMS served as the internal standard. TMS was further used as an internal standard for reporting the all chemical shifts in δ (ppm). The FT-IR spectrum for the samples was established using a Perkin Elmer Perkin Elmer Precisely 100 FT-IR spectrometer at the 400-4000 cm-1 area. Purity of all the reaction products was confirmed by TLC using aluminum plates coated with silica gel (Merck Kieselgel 60 F254).

Computational methods

3D structures of both representative compounds (6b,6h and 6j) were submitted in the mol2 format on the Pharm Mapper web server. The outputs were analyzed using the Discovery Studio (DS) visualizer. For docking, the crystal structure of MEK-1(pdb code: 1S9J) was obtained from the protein data bank ( All native ligands and water molecules associated with the protein were removed. Both representative compounds. A geometry optimization of all the compounds was performed by using Gaussian 09 1software package 1 for flexible conformations of the compounds during the docking [1]. The 2AutoDock 4.2-MGL Tools version 1.5.6 software package was utilized to carry out molecular docking analysis. Hence to identify other residual interactions of the tested compounds, a grid box (include residues within a 10.0 Å radius) large enough to accommodate the active site was constructed.

Spectra’s of substituted tetrazole derivatives

1H NMR spectra of compound 6a

FTIR spectra of compound 6a

13C NMR spectra of compound 6a

HRMS spectra of compound 6a


1H NMR spectra of compound 6b

FTIRMR spectra of compound 6b


13C NMR spectra of compound 6b

HRMS spectra of compound 6b


1H NMR spectra of compound 6c

FTIR spectra of compound 6c

13C NMR spectra of compound 6c

HRMS spectra of compound 6c


1H NMR spectra of compound 6d

FTIT spectra of compound 6d

13C NMR spectra of compound 6d

HRMS spectra of compound 6d

1H NMR spectra of compound 6e

FTIR spectra of compound 6e

13C NMR spectra of compound 6e

HRMS spectra of compound 6e


1H NMR spectra of compound 6f

FTIR spectra of compound 6f

13C NMR spectra of compound 6f

HRMS spectra of compound 6f

1H NMR spectra of compound 6g

FTIR spectra of compound 6g

13C NMR spectra of compound 6g


HRMS spectra of compound 6g

1H NMR spectra of compound 6h

FTIR spectra of compound 6h

13C NMR spectra of compound 6h


HRMS spectra of compound 6h


1H NMR spectra of compound 6i

FTIR spectra compound of 6i

13C NMR spectra of compound 6i


HRMS spectra of compound 6i


1H NMR spectra of compound 6j

FTIR spectra of compound 6j

13C NMR spectra of compound 6j

HRMS spectra of compound 6j

1H NMR spectra of compound 6k

FTIR spectra of compound 6k

13C NMR spectra of compound 6k

Reference:

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