ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis and characterization of some benzidine-based azomethine derivatives with molecular docking studies and anticancer activities

Musa Erdoğan, Ali Yeşildağ, Barış Yıldız, Burak Tüzün, and Özkan Özden

Department of Food Engineering, Faculty of Engineering and Architecture, Kafkas University, Kars, Turkey

E-mail: aliyesildag@yahoo.com

Received: 20 February 2023  Accepted: 14 July 2023

Abstract:

In this study, a benzidine-based azomethine derivate 2 with a proposed new mechanism and its two derivatives 4a-b have been designed, synthesized and characterized by ¹H, ¹³C NMR, FT-IR, and HRMS spectroscopic techniques, and their anticancer properties were investigated. The target compounds 2, 4a-b were obtained with excellent yields (91% and above) by condensation of benzidine (1) with three different aldehyde derivatives (formaldehyde, benzaldehyde 3a or p-nitrobenzaldehyde 3b) in refluxing EtOH. Surprisingly, treatment of benzidine (1) with formaldehyde afforded N⁴,N⁴,N^4',N^4'-tetrakis(ethoxymethyl)-[1,1'-biphenyl]-4,4'-diamine (2). The anticancer properties of these benzidine derivatives 2, 4a-b against two cell lines (MDA-MB-231 human breast adenocarcinoma and DLD1 human colorectal adenocarcinoma cell lines) were investigated with a colorimetric assay using the tetrazolium salt WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salts). The obtained results showed that the benzidine-based azomethine derivatives 2, 4a-b had a significant effect on the human breast cancer cell line (MDA-MB-231). Then, molecular docking calculations were made to compare the biological activities of benzidine-based azomethine derivatives 2, 4a-b against cancer proteins. ADME/T analysis was performed to examine the drug properties of benzidine-based azomethine derivatives 2, 4a-b. The compounds 2, 4a-b are promising as potential anticancer drug candidates.

Graphical Abstract

Keywords: Azomethine derivatives; Anticancer activities; MDA-MB-231; DLD1; Molecular docking; ADME/T

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-023-02981-3

Chemical Papers 77 (11) 6829–6847 (2023)