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

Synthesis of thiophene-based imine and phosphoazometine compounds: in vitro antiproliferative, antimicrobial, antioxidant, carbonic anhydrase I and II enzyme inhibition evaluations and molecular docking study

Kubra Ozturk, Muhammet Saban Tanyildizi, Harun Ciftci, and Ozlem Gundogdu Aytac

Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kırşehir Ahi Evran University, Kırşehir, Türkiye

E-mail: kubra.ozturk@ahievran.edu.tr

Received: 16 October 2024  Accepted: 27 April 2025

Abstract:

New thiophene-based imine ((E)-N,N-dimethyl-4-((thiophen-2-yl-methylene)amino)aniline) (Y6), amine (N1,N1-dimethyl-N4-(thiophen-2)-ylmethyl)benzene-1,4-diamine) (Y6a), and phosphoacomethine (diphenyl (((4-(dimethylamino)phenyl)amino)(thiophen-2-yl)methyl)phosphate) (Y6b) compounds were synthesized, and their structures were thoroughly analyzed. The synthesized compounds were determined to have antioxidant effects and strong inhibitory effects against human carbonic anhydrases I and II (hCA I and hCA II) isoforms. All compounds exhibited significant antioxidant properties, with compound Y6a showing an IC₅₀ value of 5.13 µg/mL, which was significantly lower than the IC₅₀ of ascorbic acid (17.55 µg/mL). The compounds also demonstrated potent inhibitory effects against hCA I and hCA II isoenzymes, with IC₅₀ values of 1.96 µM (Y6), 8.25 µM (Y6a), and 0.46 µM (Y6b) for hCA I, and 1.89 µM (Y6), 0.56 µM (Y6a), and 1.02 µM (Y6b) for hCA II. In addition to the experimental findings, molecular docking studies of the synthesized compounds were performed. Antimicrobial tests of the synthesized compounds were performed, and it was determined that they have antibacterial activity against bacterial strains. Additionally, all three compounds exhibited promising antiproliferative activity in the MCF-7 breast cancer cell line, with IC₅₀ values of 56.58 µM (Y6), 51.30 µM (Y6a), and 40.01 µM (Y6b). Notably, the IC₅₀ value of Y6b (40.01 µM) was found to be comparable to that of cisplatin, one of the effective chemotherapy drugs, and has the potential to be a drug or drug precursor.

Graphical abstract

Keywords: Bioinorganic Chemistry; Compound Screening; Inorganic Chemistry; Organic Chemistry; Phosphorene; Small Molecules; Phosphanate compound; Antioxidant; Antimicrobial; MCF-7 cells; Carbonic anhydrase

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04096-3

Chemical Papers 79 (7) 4735–4751 (2025)