Hybrid Compounds Containing Carvacrol Scaffold: In Vitro Antibacterial and Cytotoxicity Evaluation.

Abstract

Background: The design of hybrid compounds is a distinct approach for developing potent bioactive agents. Carvacrol, an essential oil, exhibits antimicrobial, antifungal, antioxidant, and anticancer activity, making it a good precursor for the development of compounds with potent biological activities. Some patents have reported carvacrol derivatives with promising biological activities.

Objective: This study aimed to prepare hybrid compounds containing a carvacrol scaffold with significant antibacterial and anticancer activity.

Methods: Esterification reactions between carvacrol and known pharmacophores were performed at room temperature and characterized using ¹H-NMR, ¹³CNMR, and UHPLC-HRMS. In vitro antibacterial study was determined using the microdilution assay and cytotoxicity evaluation using sulforhodamine B staining assay.

Results: The FTIR spectra of the carvacrol hybrids revealed prominent bands in the range of 1612-1764 cm^-1 and 1014-1280 cm^-1 due to (C=O) and (C-O) stretching vibrations, respectively. The structures of the carvacrol hybrids were confirmed by ¹H-NMR, ¹³C-NMR, and UHPLC-HRMS analysis, and compound 5 exhibited superior activity when compared to the hybrid compounds against the strains of bacteria used in the study. The in vitro cytotoxicity evaluation showed that compound 3 induced cytotoxicity in all the cancer cell lines; MDA (16.57 ± 1.14 μM), MCF-7 (0.47 ± 1.14 μM), and DU145 (16.25 ± 1.08 μM), as well as the normal breast cells, MCF-12A (0.75± 1.30 μM). Compound 7 did not induce cytotoxicity in the cell lines tested (IC₅₀ > 200 μM).

Conclusion: The modification of carvacrol through hybridization is a promising approach to develop compounds with significant antibacterial and anticancer activity.