Synthesis, antibacterial and antifungal activities of naphthoquinone derivatives: a structure–activity relationship study

Abstract

The synthesis of 1,4-naphthoquinone derivatives is of great interest since these compounds exhibit strong activity as antimalarial, antibacterial, antifungal and anticancer agents. A series of 50 naphthoquinone derivatives was synthesized and evaluated for antibacterial and antifungal activity against Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Candida krusei, Candida parapsilosis and Cryptococcus neoformans using the broth microdilution method. The Candida species were the most susceptible microorganisms. Halogen derivatives of 1,4-naphthoquinone presented strong activity, e.g., 2-bromo-5-hydroxy-1,4-naphthoquinone, which exhibited inhibition at an MIC of 16 lg/ mL in S. aureus, and 2-chloro-5,8-dihydroxy-1,4-naphthoquinone, with an MIC of 2 lg/mL in C. krusei. These compounds showed higher activity against fungi, but the antibacterial activities were very low. The study of structure-activity relationships is very important in the search for new antimicrobial drugs due to the limited therapeutic arsenal.

Recent advances in allelopathy for weed control: from knowledge to applications

“…Furthermore, more complex quinones (naphthoquinones) in which carbonyl groups are present in the para position have enhanced antimicrobial activity. However, the presence of any aliphatic chain substitution decreases the activities in all cases studied …”

“…In most cases, the biological properties of quinones are related to their redox and acid–base properties. Quinones often exhibit strong biological effects that include antimalarial, antibacterial and antifungal activities in both aerobic and anaerobic organisms …”

“…This is related to their ability to accept one or two electrons and to form reactive radical intermediates, which are responsible for oxidative stress in cells. Furthermore, other mechanisms have been reported, depending on the structure of the quinone, for example, inhibition of topoisomerases in cancer cells via a 1,4‐Michael addition involving the nucleophilic thiol or DNA degradation . This mechanism has not been verified in plant cells.…”

Structure‐activity relationship studies on naphthoquinone analogs. The search for new herbicides based on natural products

“…Twelve derivatives (from 2–16 carbon atoms) were prepared according to the reported procedure (Fig. ) . 5‐ O ‐acyl plumbagins were obtained in moderate‐high yield (20–70%).…”

“…Naphthoquinones constitute the largest and most diverse group of plant secondary metabolites and they have been known for a long time for their use as dyes and for their biological properties . It is worth noting that cellular biological and pharmacological properties have been reported for these compounds in numerous studies, including wound healing, antifungal, anti‐inflammatory, antioxidant, leishmanicidal and antitumor activities . On the other hand, little is known about their biological activity in higher plants and their mode of action.…”