Current Topics in Medicinal Chemistry - Volume 22, Issue 12, 2022

Background: Microbial resistance has become a worldwide public health problem and may lead to morbidity and mortality in affected patients. Objectives: Therefore, this work aimed to evaluate the antibacterial activity of quinone-4- oxoquinoline derivatives. Methods: These derivatives were evaluated against Gram-positive and Gram-negative bacteria by their antibacterial activity, anti-biofilm, and hemolytic activities and in silico assays. Results: The quinone-4-oxoquinoline derivatives presented broad-spectrum antibacterial activities and, in some cases, were more active than commercially available reference drugs. These compounds also inhibited bacterial adhesion, and the assays revealed seven non-hemolytic derivatives. The derivatives seem to cause damage to the bacterial cell membrane, and those containing the carboxyl group at the C-3 position of the 4-quinolonic nucleus were more active than those containing a carboxyethyl group. Conclusion: The isoquinoline-5,8-dione nucleus also favored antimicrobial activity. The study showed that the target of the derivatives must be a non-conventional hydrophobic allosteric binding pocket on the DNA gyrase enzyme.

Acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), is one of the leading causes of human deaths. The advent of different anti-HIV drugs has turned AIDS/HIV from a deadly infection to chronic and manageable disease. However, the development of multidrug-resistant viruses, along with the severe side effects of anti-HIV agents, has compromised their efficacy and limited the treatment options. Indoles, the most common frameworks in the bioactive molecules, represent attractive scaffolds for designing and developing novel drugs. Indole derivatives are potent inhibitors of HIV enzymes such as reverse transcriptase, integrase, and protease. Furthermore, some indole-based agents, like delavirdine, have already been applied in clinics or are under clinical evaluations for the treatment of AIDS/HIV, revealing that indole moiety is a useful template for the development of anti-HIV agents. This review focuses on the recent advancement in indole derivatives, including indole alkaloids, hybrids, and dimers with anti-HIV potential, covering articles published between 2010 and 2020. The chemical structures, structure-activity relationship, and mechanisms of action are also discussed.

Flavonoids, a wide variety of phenolic secondary metabolites, are found in almost all plant families in the leaves, stems, roots, flowers, and seeds. Flavonoids could exert antibacterial activity via damaging the cytoplasmic membrane, inhibiting energy metabolism, and inhibiting the synthesis of nucleic acids, so flavonoids are considered constitutive antibacterial substances. This review aims to outline the recent advances of natural-derived flavonoids, including flavonoid glycosides with antibacterial potential to provide novel antibacterial lead hits/candidates, covering articles published between January 2016 and July 2021.

Staphylococcus aureus (S. aureus), an important pathogen of both humans and animals, can cause a variety of infections at any site of the body. The evolution of S. aureus resistance is notorious, and the widespread of drug-resistant S. aureus, especially methicillin-resistant S. aureus (MRSA), has made the treatment difficult in recent decades. Nowadays, S. aureus is among the leading causes of bacterial infections, creating an urgent need for the development of novel antibacterial agents. Ciprofloxacin, characterized by high clinical efficacy, is a broad-spectrum antibacterial agent with frequency of prescription for various Gram-positive and Gram-negative pathogens, many of which are resistant to a wide range of antibiotics. However, the long-term and widespread use of this antibiotic has led to the emergence of ciprofloxacin-resistant pathogens, and ciprofloxacin- resistant S. aureus has been noted in clinical practice. Ciprofloxacin hybrids have been recognized as advanced chemical entities to simultaneously modulate multiple drug targets in bacteria, so ciprofloxacin hybrids have the potential to overcome drug resistance. The present review provides an overview of ciprofloxacin hybrids with anti-S. aureus potential that has been reported in the last decade with an emphasis on their structure-activity relationships and mechanisms of action.

Bacterial infections cause substantial morbidity and mortality across the world and pose serious threats to humankind. Drug resistance, especially multidrug resistance resulting from different defensive mechanisms in bacteria, is the leading cause of the failure of chemotherapy, making it an urgent need to develop more effective antibacterials. Quinazoline and quinazolinone frameworks have received considerable attention due to their diversified therapeutic potential. In particular, quinazoline/quinazolinone hybrids can exert antibacterial activity through various mechanisms and are useful scaffolds for the discovery of novel antibacterials. This review principally emphasizes the antibacterial potential, structure-activity relationships (SARs), and mechanism of action of quinazoline and quinazolinone hybrids, covering articles published between 2017 and 2021.