Antibacterial and anticancer profiling of new benzocaine derivatives: Design, synthesis, and molecular mechanism of action. Issue 4 (31st January 2022)

• Record Type: Journal Article
• Authors: El‐Zahabi, Heba S. A.; Nossier, Eman S.; Mousa, Safya M.; Hassan, Heba; Shalaby, AL Shimaa G.; Arafa, Reem K.
• Is Part Of: Archiv der Pharmazie. Volume 355:Issue 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-31
• Subjects: antibacterial activity -- anticancer activity -- benzocaine derivatives -- DNA gyrase -- DNA topoisomerase; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202100451
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: The need for new chemotherapeutics to overcome development of resistance merits research to discover new agents. Benzocaine derivatives are essential compounds in medicinal chemistry due to their various biological activities including antibacterial and anticancer activities. Therefore, this study focuses on the synthesis of new benzocaine derivatives 3a–e, 6, 7a and 7b, 8, 10–14, and 16a–d and their in vitro evaluation as antibacterial agents against gram +ve and –ve strains and as anticancer agents against HepG‐2, HCT‐116, and MCF‐7 human cancer cell lines. The obtained results demonstrated that thiazolidines 6 and 7b showed higher antibacterial and anticancer activity in comparison with the reference drugs. In addition, 6 and 7b showed high potency as inhibitors toward their biological targets, that is DNA gyrase and human topoisomerase IIα, as compared to the reference standard drugs novobiocin and etoposide, respectively. Molecular docking demonstrated that both compounds could identify the active site of their target enzymes and develop effective binding interactions. Absorption, distribution, metabolism and elimination (ADME) and drug‐likeness predictions of both compounds showed that they both have good ADME profiles and no structural alerts that might cause toxicity. Based on this, 6 and 7b could serve as lead compounds for the design of more potent antibacterial and anticancer agents. Abstract : New benzocaine derivatives were designed, synthesized, and evaluated as antibacterial agents against gram +ve and –ve strains and as anticancer agents against HepG‐2, HCT‐116, and MCF‐7 human cancer cells. Thiazolidines 6 and 7b showed higher antibacterial and anticancer activity than their reference drugs and potently inhibited their biological targets, that is DNA gyrase and human topoisomerase IIα.