Current Topics in Medicinal Chemistry - Volume 18, Issue 1, 2018

The development of new antimicrobial drugs is a very challenging task owing to the rapidly developing drug resistance among the existing drugs. The hybridization of active and novel compounds is a commonly used approach to combat this situation. The azo linkage (N=N) is successfully used to link two bioactive moieties to enhance the therapeutic effects. The hybrid derivatives linked by azo linkage have shown their activity by acting on target proteins in microorganisms, cell wall inhibitors, DHPS inhibitors, RNA Editing Ligase 1 inhibitors, the general protein secretory (Sec) pathway inhibitors, neuraminidase inhibitors, etc. The current review covers the general enzymes and regulatory pathways in microorganisms targeted by diazenyl compounds and recent developments pertaining to diazenyl derivatives as antimicrobial agents during the last five years. This information will prove useful to the researchers for the development of novel antimicrobial agents by slight modifications in active derivatives with improved activities.

Microbial contamination still remains a major issue of the modern era, due to the widespread of drug-resistant pathogens. This has prompted researchers to come up with novel antimicrobial systems that could overcome antibiotic-resistance. In this context, nature can provide inestimable source of inspiration to design high-performance multifunctional materials with potent activity against drug-resistant pathogens. Actually, integrating the bio-inspired-approach with nanotechnology can provide cutting-edge solutions for drug-resistant infections. In this context, this review will examine recent advances in the development of bio-inspired antimicrobial nanostructures. Advantages of bioinspired approach to nanomaterials over conventional routes have been highlighted. Generally, bionspired synthesis can be carried out either by mimicking the functions of natural materials/ structures or by mimicking the biological processes employed to produce substances or materials. The review provides an overview of both strategies as applied to the synthesis of inorganic, organic as well as hybrid nanostructures. Antimicrobial efficacy and biological properties of these systems have been highlighted. Antimicrobial and antibiofouling nanostructured surfaces are also discussed.

The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs are important to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics.

Background: Thiazole and benzothiazole derivatives, as well as thiazolidinones are very important scaffolds in medicinal chemistry. Literature has revealed that they possess a wide spectrum of biological activities including antimicrobial activity. Objective: The goal of this paper is the designing of new benzothiazole based thiazolidinones and the evaluation of their biological activities. Methods: The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was evaluated using the method of microdilution. Results: The twelve newly synthesized compounds showed antimicrobial properties. All compounds appeared to be more active than ampicillin in most studied strains and in some cases, more active than streptomycin. Antifungal activity, in most cases was also better than the reference drugs ketoconazole and bifonazole. The prediction of cytotoxicity revealed that the synthesized compounds were not toxic (LD50 350-1000 mg/kg of body weight). Docking studies on the antibacterial activity confirmed the biological results. Conclusion: The twelve new compounds were synthesized and studied for their antimicrobial activity. The compounds appeared to be promising antimicrobial agents and could be the lead compounds for new, more potent drugs. According to the docking prediction, the compounds could be MurB inhibitors.

Background: The impact of fungal infections on human health has increased considerably within a past few decades. Although drugs with antifungal properties are available, but they are less effective and are associated with side effects. Objective and Method: To screen the bacterial isolates from Sesamum indicum and to investigate the antifungal activity of the screened bacterial isolates against Aspergillus sp. Co-culture assay and agar overlay were used to scrutinize the anti-Aspergillus activity. Furthermore, optimization of media and growth conditions to enhance the production of anti-Aspergillus compound. Results: Several bacterial cultures were isolated from Sesamum indicum rhizosphere collected from Mandi (H.P.) India. These bacterial cultures were assayed for antifungal activity against Aspergillus species i.e. A. fumigatus and A. niger. Two most potent strains were chosen for more detailed analyses. The biochemical characterization and 16S ribosomal RNA sequencing revealed that Burkholderia sp. strain RC1 and Acinetobacter pittii strain RC2 exhibit strong similarity (100%) with Burkholderia sp. SR2-07 and Acinetobacter sp. strain 3-59. Additionally, it was also validated that RC1 and RC2 showed significant difference in the production of anti-Aspergillusactivity under altered growth conditions. Conclusion: Results from this study recommend that plant rhizosphere remains a rich hotspot for delivering a novel antifungal compounds.