Synthesis of and Biological Study of 7-Benzyl-3-aminobenzimidazo[3,2- a]quinolinium Chloride (ABQ-48: NSC D-763307) and 7-benzyl-3- nitrobenzimidazo[3,2-a]quinolinium Chloride (NBQ 48: NSC D-763303)

Title:Synthesis of and Biological Study of 7-Benzyl-3-aminobenzimidazo[3,2- a]quinolinium Chloride (ABQ-48: NSC D-763307) and 7-benzyl-3- nitrobenzimidazo[3,2-a]quinolinium Chloride (NBQ 48: NSC D-763303)

Volume: 10 Issue: 4

Author(s): Osvaldo Cox, Christian Velez, Vineet Kumar, Sanjay V. Malhotra, Luis A. Rivera, Wigberto J. Hernandez, Jose R. Martinez, Marisol Cordero and Beatriz Zayas

Affiliation:

Keywords: Cancer, quinolinium salts, synthesis.

Abstract: Benzazolo[3,2-a]quinolium salts (BQS) are cationic quaternary alkaloids with similar structure to the anticancer agent ellipticine. This study describes the synthesis and screen, at the experimental concentration of 10 mM, utilizing the 60 cell line anti-cancer screening of two BQS, namely, 7-benzyl-3- aminobenzimidazo[3,2-a]quinolinium chloride (ABQ-48: NSC D-763307) and the corresponding 7-benzyl-3- nitrobenzimidazo[3,2-a]quinolinium chloride (NBQ 48: NSC D-763303). Compound ABQ-48: NSC D-763307 was also screened in the 5-dose NCI panel. These compounds differ in the presence of an amino or nitro substituent at the 3- position in ring A. The data show that ABQ 48 with electron donating amino group at position 3 in ring A is highly effective in the growth inhibition in several cancer cell lines. However, its analog NBQ 48 which has an electron withdrawing nitrogen group at this position has negligible effect in most of the cell lines. In particular, ABQ 48 shows >90% growth inhibition in KM12, U251 & SK-MEL-5; and >70% growth inhibition in several cell lines. As per the NCI’s screening criteria ABQ 48 showed better than 60% growth inhibition in at least eight tumor cell lines, and thus, selected for the five dose response study. It is therefore concluded that the biological activity of these compounds is greatly affected by their electron donating properties. Additionally, this work describes the complete proton and carbon-13 chemical shifts assignments using 1D and 2D nuclear magnetic resonance techniques.

Cite this article as:

Cox Osvaldo, Velez Christian, Kumar Vineet, V. Malhotra Sanjay, A. Rivera Luis, J. Hernandez Wigberto, R. Martinez Jose, Cordero Marisol and Zayas Beatriz, Synthesis of and Biological Study of 7-Benzyl-3-aminobenzimidazo[3,2- a]quinolinium Chloride (ABQ-48: NSC D-763307) and 7-benzyl-3- nitrobenzimidazo[3,2-a]quinolinium Chloride (NBQ 48: NSC D-763303), Current Bioactive Compounds 2014; 10 (4) . https://dx.doi.org/10.2174/1573407210666141126204355