Work

A Sustainable Synthesis of Novel 2-(3,4-Disubstituted phenyl)benzoxazole Derivatives and Their Antiproliferative and Antibacterial Evaluation

Year: 2025

Type: article

Abstract: This study describes the synthesis of O-alkylated benzaldehydes 1–8, Schiff bases 9–28, and benzoxazole derivatives 29–48 using microwave, ultrasound, and mechanochemical reactions, as well as reactions in deep eutectic solvents in excellent yields, and their antiproliferative and antibacterial activities. The in vitro evaluation of antiproliferative activity for the newly synthesised benzoxazole derivatives 29–48 against a diverse panel of human cancer cell lines, such as LN-229, Capan-1, HCT-116, NCI-H460, DND-41, HL-60, K-562, and Z-138 demonstrated that the majority of these benzoxazole derivatives displayed promising anticancer activity, particularly against non-small cell lung cancer (NSCLC) cells (NCI-H460). Notably, several derivatives showed enhanced activity compared to the included reference drug, etoposide. Considering the influence of substituents at position 5 of the benzoxazole ring and positions 3 and 4 of the phenyl ring on the antiproliferative activity, it is evident that derivatives 41–48 bearing a methoxy group at position 3 generally exhibit higher activity compared to compounds 29–40, which lack substitution at position 3. Furthermore, derivatives substituted at position 4 with a morpholine substituent, as well as those with an N,N-diethyl group, exhibited higher activity compared to other evaluated benzoxazole derivatives. The in vitro antibacterial evaluation against Gram-positive and Gram-negative bacteria revealed that benzoxazole derivative 47 exhibited notable activity, against the Gram-negative bacterium Pseudomonas aeruginosa (MIC = 0.25 μg/mL) and the Gram-positive bacterium Enterococcus faecalis (MIC = 0.5 μg/mL). The results point out that this class of benzoxazoles can be efficiently synthesized using eco-friendly methods and represent promising candidates for further design and optimization aimed at developing potent antiproliferative agents.

Source: Molecules

DOI: 10.3390/molecules30081767

Authors: Anja Rakas, Leentje Persoons, Dirk Daelemans, Dajana Kučić Grgić, Tatjana Gazivoda Kraljević

Institutions: University of Zagreb, Rega Institute for Medical Research, KU Leuven, University North

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258