Preliminary Insight of Pyrrolylated-Chalcones as New Anti-Methicillin-Resistant Staphylococcus aureus (Anti-MRSA) Agents

Bacterial infections are regarded as one of the leading causes of fatal morbidity and death in patients infected with diseases. The ability of microorganisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), to develop resistance to current drugs has evoked the need for a continuous search for new drugs with better efficacies. Hence, a series of non-PAINS associated pyrrolylated-chalcones (1–15) were synthesized and evaluated for their potency against MRSA. The hydroxyl-containing compounds (8, 9, and 10) showed the most significant anti-MRSA efficiency, with the MIC and MBC values ranging from 0.08 to 0.70 mg/mL and 0.16 to 1.88 mg/mL, respectively. The time-kill curve and SEM analyses exhibited bacterial cell death within four hours after exposure to 9, suggesting its bactericidal properties. Furthermore, the docking simulation between 9 and penicillin-binding protein 2a (PBP2a, PDB ID: 6Q9N) suggests a relatively similar bonding interaction to the standard drug with a binding affinity score of −7.0 kcal/mol. Moreover, the zebrafish model showed no toxic effects in the normal embryonic development, blood vessel formation, and apoptosis when exposed to up to 40 µM of compound 9. The overall results suggest that the pyrrolylated-chalcones may be considered as a potential inhibitor in the design of new anti-MRSA agents.     

Nipecotic Acid Derivatives as Potent Agents against Neurodegeneration: A Preliminary Study

Alzheimer’s Disease (AD) is a common neurodegenerative disorder characterized by memory loss and cognitive impairment. Its pathology has not been fully clarified and therefore highly effective treatments have not been obtained yet. Almost all the current treatment options aim to alleviate only the symptoms and not to eliminate the disease itself. Acetylcholinesterase inhibitors are the main therapeutic agents against AD, whereas oxidative stress and inflammation have been found to be of great significance for the development and progression of neurodegeneration. In this work, ethyl nipecotate (ethyl-piperidine-3-carboxylate), a heterocyclic carboxylic acid derivative, which acts as a GABA reuptake inhibitor and has been used in research for diseases involving GABAergic neurotransmission dysfunction, was amidated with various carboxylic acids bearing antioxidant and/or anti-inflammatory properties (e.g., ferulic acid, sinapic acid, butylated hydroxycinnamic acid). Most of our compounds have significant antioxidant potency as lipid peroxidation inhibitors (IC₅₀ as low as 20 μΜ), as oxidative protein glycation inhibitors (inhibition up to 57%), and act as DPPH reducing agents. Moreover, our compounds are moderate LOX inhibitors (up to 33% at 100 μΜ) and could reduce rat paw edema induced by carrageenan by up to 61%. Finally, some of them possessed inhibitory activity against acetylcholinesterase (IC₅₀ as low as to 47 μΜ). Our results indicate that our compounds could have the potentiality for further optimization as multi-targeting agents directed against AD.     

Alternative Functionalization of Hydrogen-Bonded Diketopyrrolopyrrole Derivatives**

Diketopyrrolopyrrole (DPP) derivatives with thiophene capping rings are widely used as semiconductors in organic electronics. Their optoelectronic properties can be adjusted by adding different electroactive groups or by extending the conjugation of the central core, as well as by regulating their self-assembly through noncovalent interactions. One effective strategy demonstrated to improve the performance and morphology of organic solar cells is incorporating hydrogen-bonding units into DPPs. While the functionalization of the DPP lactams and the coupling of aromatic units to the thiophene rings are the most common procedures to tune the properties of such derivatives, modifying the thiophene capping units with hydrogen-bonding groups is a challenging synthetic task. Despite this difficulty, incorporating amide-containing substituents into the thiophene rings of single core thiophene-capped DPP derivatives could yield exciting results, as the advantages of having hydrogen-bonded π-conjugated systems based on these modified DPPs have not been explored thoroughly. This work reports on an efficient method for synthesizing such derivatives.     

Nopol-Based Quinoline Derivatives as Antiplasmodial Agents

Malaria remains a significant cause of morbidity and mortality in Sub-Saharan Africa and South Asia. While clinical antimalarials are efficacious when administered according to local guidelines, resistance to every class of antimalarials is a persistent problem. There is a constant need for new antimalarial therapeutics that complement parasite control strategies to combat malaria, especially in the tropics. In this work, nopol-based quinoline derivatives were investigated for their inhibitory activity against Plasmodium falciparum, one of the parasites that cause malaria. The nopyl-quinolin-8-yl amides (2–4) were moderately active against the asexual blood stage of chloroquine-sensitive strain Pf3D7 but inactive against chloroquine-resistant strains PfK1 and PfNF54. The nopyl-quinolin-4-yl amides and nopyl-quinolin-4-yl-acetates analogs were generally less active on all three strains. Interesting, the presence of a chloro substituent at C7 of the quinoline ring of amide 8 resulted in sub-micromolar EC₅₀ in the PfK1 strain. However, 8 was more than two orders of magnitude less active against Pf3D7 and PfNF54. Overall, the nopyl-quinolin-8-yl amides appear to share similar antimalarial profile (asexual blood-stage) with previously reported 8-aminoquinolines like primaquine. Future work will focus on investigating the moderately active and selective nopyl-quinolin-8-yl amides on the gametocyte or liver stages of Plasmodium falciparum and Plasmodium vivax.     

Pyridyl Methylsulfinyl Benzimidazole Derivatives as Promising Agents against Giardia lamblia and Trichomonas vaginalis

Protozoan parasites, such as Giardia lamblia and Trichomonas vaginalis, cause the most prevalent infections in humans in developing countries and provoke significant morbidity and mortality in endemic countries. Despite its side-effects, metronidazole is still the drug of choice as a giardiacidal and trichomonacidal tissue-active agent. However, the emergence of metronidazole resistance and its evolved strategies of parasites to evade innate host defenses have hindered the identification and development of new therapeutic strategies against these parasites. Here, we tested five synthesized benzimidazole derivatives as possible drugs for treating giardiasis and trichomoniasis, probing the bifunctional enzyme glucose 6-phosphate dehydrogenase::6-phosphogluconolactone from G. lamblia (GlG6PD::6PGL) and T. vaginalis (TvG6PD::6PGL) as a drug target. The investigated benzimidazole derivatives were H-B2M1, H-B2M2, H₂N-BZM6, O₂N-BZM7, and O₂N-BZM9. The recombinant enzymes were used in inhibition assays, and in silico computational predictions and spectroscopic studies were applied to follow the structural alteration of the enzymes and identify the possible mechanism of inhibition. We identified two potent benzimidazole compounds (O₂N-BZM7 and O₂N-BZM9), which are capable of inhibiting both protozoan G6PD::6PGL enzymes and in vitro assays with these parasites, showing that these compounds also affect their viability. These results demonstrate that other therapeutic targets of the compounds are the enzymes GlG6PD::6PGL and TvG6PD::6PGL, which contribute to their antiparasitic effect and their possible use in antigiardial and trichomonacidal therapies.     

New Thiophene Derivatives as Antimicrobial Agents

Phenacylbromide derivatives constitute a multilateral group of precursors for the synthesis of numerous heterocycles of organic compounds. Briefly, 5‐(2‐bromo‐acetyl)‐substituted‐thiophene derivative has been used as a synthon for synthesis of new thiophene‐containing compounds through the reaction with nucleophilic nitrogen compounds and thioamides. The suggested structures of the newly synthesized thiophene compounds were confirmed and assured with different spectroscopic tools and with CHN elemental analysis. Additionally, the antimicrobial activity of these thiophene compounds was recorded to investigate their potency against various types of bacteria and fungi. Results showed that these compounds exhibit significant inhibitory activity against the growth of tested bacterial and fungal strains and that some derivatives were more potent than the employed reference drugs.     

Carbazole Derivatives as Potential Antimicrobial Agents

Microbial infection is a leading cause of death worldwide, resulting in around 1.2 million deaths annually. Due to this, medicinal chemists are continuously searching for new or improved alternatives to combat microbial infections. Among many nitrogen-containing heterocycles, carbazole derivatives have shown significant biological activities, of which its antimicrobial and antifungal activities are the most studied. In this review, miscellaneous carbazole derivatives and their antimicrobial activity are discussed (articles published from 1999 to 2022).     

Hamamelitannin Analogues that Modulate Quorum Sensing as Potentiators of Antibiotics against Staphylococcus aureus

The modulation of bacterial communication to potentiate the effect of existing antimicrobial drugs is a promising alternative to the development of novel antibiotics. In the present study, we synthesized 58 analogues of hamamelitannin (HAM), a quorum sensing inhibitor and antimicrobial potentiator. These efforts resulted in the identification of an analogue that increases the susceptibility of Staphylococcus aureus towards antibiotics in vitro, in Caenorhabditis elegans, and in a mouse mammary gland infection model, without showing cytotoxicity.     

对苯二胺类防老剂的合成

介绍和评述了合成对苯二胺类防老剂的方法及所用催化体系。参考文献３２篇。     

Synthesis of Novel Flavanone Derivatives and Their Anti Staphylococcus aureus Evaluation

The authors synthesized two novel flavanones bearing iso-pentenyl side chain and evaluated their anti Staphylococcus aureus(S. aureus) activity. The target compounds 7a[2-5'-(1",2"-dimethylallyl)-2'-methoxy-4',5,7-tetrahydroxyflavanone] and 7b[2-5'-(1",2"-dimethylallyl)-3'-methoxy-4',5,7-tetrahydroxyflavanone] were synthesized respectively through total four steps starting from 2,4,6-trihydroxy acetophenone(3) and the corresponding iso-pentenyl substituted benzaldehyde(1), in which the 1,2-dimethyl-2-propenyl group had been introduced previously via abnormal Claisen rearrangement. The bioactivities of the two flavanones against S. aureus strains ATCC 25923, 29213, and MRSA 252 were evaluated, showing the same minimum inhibitory concentration(MIC) value of 16 μg/mL.     

Rhodium Nanoparticles as a Novel Photosensitizing Agent in Photodynamic Therapy against Cancer

Photodynamic therapy (PDT) is a promising alternative treatment for different types of cancer due to its high selectivity, which prevents healthy tissues from being damaged. The use of nanomaterials in PDT has several advantages over classical photosensitizing agents, due to their unique properties and their capacity for functionalization. Especially interesting is the use of metallic nanoparticles, which are capable of absorbing electromagnetic radiation and either transferring this energy to oxygen molecules for the generation of reactive oxygen species (ROS) or dissipating it as heat. Although previous reports have demonstrated the capacity of Rh derivatives to serve as anti-tumor drugs, to the best of our knowledge there have been no studies on the potential use of small-sized Rh nanoparticles as photosensitizers in PDT. In this study, 5 nm Rh nanoparticles have been synthesized and their potential in PDT has been evaluated. The results show that treatment with Rh nanoparticles followed by NIR irradiation induces apoptosis in cancer cells through a p53-independent mechanism.     

Antibacterial activity of long-chain fatty alcohols against Staphylococcus aureus

The antibacterial activity against Staphylococcus aureus of long-chain fatty alcohols was investigated, with a focus on normal alcohols. The antibacterial activity varied with the length of the aliphatic carbon chain and not with the water/octanol partition coefficient. 1-Nonanol, 1-decanol and 1-undecanol had bactericidal activity and membrane-damaging activity. 1-Dodecanol and 1-tridecanol had the highest antibacterial activity among the long-chain fatty alcohols tested, but had no membrane-damaging activity. Consequently, it appears that not only the antibacterial activity but also the mode of action of long-chain fatty alcohols might be determined by the length of the aliphatic carbon chain.     

Design of Photosensitizing Agents for Targeted Antimicrobial Photodynamic Therapy

Photodynamic inactivation of microorganisms has gained substantial attention due to its unique mode of action, in which pathogens are unable to generate resistance, and due to the fact that it can be applied in a minimally invasive manner. In photodynamic therapy (PDT), a non-toxic photosensitizer (PS) is activated by a specific wavelength of light and generates highly cytotoxic reactive oxygen species (ROS) such as superoxide (O²⁻, type-I mechanism) or singlet oxygen (¹O₂*, type-II mechanism). Although it offers many advantages over conventional treatment methods, ROS-mediated microbial killing is often faced with the issues of accessibility, poor selectivity and off-target damage. Thus, several strategies have been employed to develop target-specific antimicrobial PDT (aPDT). This includes conjugation of known PS building-blocks to either non-specific cationic moieties or target-specific antibiotics and antimicrobial peptides, or combining them with targeting nanomaterials. In this review, we summarise these general strategies and related challenges, and highlight recent developments in targeted aPDT.     

Synthesis of Novel Quinazoline Derivatives as Antimicrobial Agents

Quinazoline isothiocyanate 1 reacts with various nucleophiles(nitrogen nucleophiles,oxygen nucleophiles and sulphur nucleophiles)to afford heterocyclic systemes 2-13,Also,the [4 2] cycloaddition reaction of 1 with phenyl isocyanate,benzylidene aryl amine and cinnamic acid derivatives gave novel heterocyclic compounds 14-16,Moreover,the reaction of 1 with active methylene compounds under Michael reaction conditions also was investigated to yield 17 and 18 and it was found that all these reactions proceede via isothiocyanate heterocyclization to furnish non-condensed heterocyclic compoundes,Some of the newly synthesized compounds were tested for their antimicrobial activities.     

Electrochemical Evaluation of Diketopyrrolopyrrole Derivatives for Nonaqueous Redox Flow Batteries

Redox flow batteries (RFBs) employing nonaqueous electrolytes could potentially operate at much higher cell voltages, and therefore afford higher energy and power densities, than RFBs employing aqueous electrolytes. The development of such high-voltage nonaqueous RFBs requires anolytes that are electrochemically stable, especially in the presence of traces of oxygen and/or moisture. The inherent atmospheric reactivity of anolytes mandates judicious molecular design with high electron affinity and electrochemical stability. In this study, diketopyrrolopyrrole (DPP)-based TDPP-Hex-CN₄ is proposed as a stable redox-active molecule for anolytes in nonaqueous organic RFBs. We demonstrate organic RFBs using TDPP-Hex-CN₄ as anolyte with unisol blue (UB) 1,4-bis(isopropylamino)anthraquinone and 1,4-di-tert-butyl-2,5-bis(2-methoxyethoxy)benzene (DBBB) as catholytes. Cyclic voltammetry measurements with scans repeated over 200 cycles were performed to establish the electrochemical stability of the redox pairs. Symmetric flow-cell studies show that TDPP-Hex-CN₄ exhibits stable capacity up to 700 cycles. Redox flow cells employing TDPP-Hex-CN₄ /UB and TDPP-Hex-CN₄/DBBB as redox pairs demonstrate that DPP derivatives are propitious materials for anolytes in all organic nonaqueous RFBs.     

Antiinfective properties of ursolic acid-loaded chitosan nanoparticles against Staphylococcus aureus

The present study aimed to synthesize ursolic acid-loaded chitosan nanoparticles (UA-Ch-NPs) as an antiinfective agent against 21 Staphylococcus aureus isolates. The UA-Ch-NPs were synthesized by a simple method and then characterized by TEM, FTIR, DLS-zeta potential, and XRD analyses. According to the characterization results, highly dispersed spherical nanoparticles with a mean diameter of 258 nm and a zeta potential of + 40.1 mV were developed. The antibacterial properties of UA-Ch-NPs were investigated and their inhibitory effect on biofilm formation was demonstrated by AFM. Finally, the expression levels of icaA and icaD were measured using real-time PCR. Results indicated that the minimum inhibitory concentration (MIC) of UA and UA-Ch-NPs against S. aureus was 64 and 32 µg/mL, respectively. The treatment of bacterial cells with UA-Ch-NPs significantly decreased the expression of icaA and icaD genes which are engaged in biofilm formation. Our results indicated that UA-Ch-NPs could be a promising material for antibacterial and antibiofilm applications.