Dual Antimicrobial and Anticancer Activity of Membrane-Active Peptide BP52.

The linear undecapeptide BP52 was previously reported to have antibacterial activity against phytopathogenic bacteria species. Due to the structural similarities to naturally occurring cationic helical antimicrobial peptides, it was speculated that this peptide could potentially target microbial pathogens and cancer cells found in mammals. Consequently, this study aims to further investigate the structural and biological properties of this peptide.

Identification of novel phenylalanine derivatives bearing a hydroxamic acid moiety as potent quorum sensing inhibitors.

Phenylalanine derivatives are a well-known small moiety responsible for controlling the virulence factors of several bacteria. Herein, for the first time, we report novel structures of phenylalanine derivatives bearing a hydroxamic acid moiety which were designed, synthesized, and evaluated for use as quorum sensing inhibitors. Biological results reveal that six compounds showed good quorum sensing inhibitors properties with an IC ranging from 7.

Determination of drug-related problems among type 2 diabetes outpatients in a hospital in Vietnam: A cross-sectional study.

Introduction: Drug-related problems (DRPs) are common in clinical practice and occur at all stages of the medication process. The major factor contributing to DRPs is prescription, although patients' poor adherence to treatment is also a significant factor. This study evaluated type 2 diabetes outpatients in a hospital in Vietnam for drug-related problems (DRPs) and related variables.

Drug Discovery and Development on Pma1, Where Are We Now? A Critical Review from 1995 to 2022.

Plasma membrane H -ATPase (Pma1) is an enzyme uniquely found in plants and fungi. The enzyme controls the nutrient uptake of plants and fungi via an electrochemical gradient processes, which is essential for their survival. Inhibiting Pma1, therefore, constitutes an alternative antifungal target void of toxicity to humans.

Correction: Benzo[]thiazole-2-thiol bearing 2-oxo-2-substituted-phenylethan-1-yl as potent selective quorum sensing inhibitors of Gram-negative bacteria.

[This corrects the article DOI: 10.1039/D1RA03616E.].

Benzo[]thiazole-2-thiol bearing 2-oxo-2-substituted-phenylethan-1-yl as potent selective quorum sensing inhibitors of Gram-negative bacteria.

Quorum sensing is a well-known term for describing bacterial cell-cell communication. Bacteria use quorum sensing pathways to respond to external factors such as nutrient availability, defense mechanisms, and coordinate host toxic behaviors such as biofilm formation, virulence production, and other pathogenesis. Discovery of novel compounds which inhibit quorum sensing without being antibiotic are currently emerging fields.

Multiple roles of ribosomal antimicrobial peptides in tackling global antimicrobial resistance.

In the last century, conventional antibiotics have played a significant role in global healthcare. Antibiotics support the body in controlling bacterial infection and simultaneously increase the tendency of drug resistance. Consequently, there is a severe concern regarding the regression of the antibiotic era.

Application of the All-Hydrocarbon Stapling Technique in the Design of Membrane-Active Peptides.

The threats of drug resistance and new emerging pathogens have led to an urgent need to develop alternative treatment therapies. Recently, considerable research efforts have focused on membrane-active peptides (MAPs), a category of peptides in drug discovery with antimicrobial, anticancer, and cell penetration activities that have demonstrated their potential to be multifunctional agents. Nonetheless, natural MAPs have encountered various disadvantages, which mainly include poor bioavailability, the lack of a secondary structure in short peptides, and high production costs for long peptide sequences.

Design, Synthesis and Evaluation of Novel (E)-N'-((1-(4-chlorobenzyl)-1H-indol-3-yl)methylene)-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides as Antitumor Agents.

Background: Herein, we have designed and synthesized a series of the novel (E)-N'-((1-(4-chlorobenzyl)- 1H-indol-3-yl)methylene)-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides (5) as potent small molecules activating procaspase- 3. The compounds were designed by the amalgamation of structural features of PAC-1 (the first procaspase-3 activator) and oncrasin-1, one potential anticancer agent.

Methods: The target acetohydrazides (5a-m) were prepared via the Niementowski condensation of anthranilic acid (1a) or 5-substituted-2-aminobenzoic acid (1b-m) and formamide.

Amide bond formation in aqueous solution: direct coupling of metal carboxylate salts with ammonium salts at room temperature.

Herein, we report a green, expeditious, and practically simple protocol for direct coupling of carboxylate salts and ammonium salts under ACN/HO conditions at room temperature without the addition of tertiary amine bases. The water-soluble coupling reagent EDC·HCl is a key component in the reaction. The reaction runs smoothly with unsubstituted/substituted ammonium salts and provides a clean product without column chromatography.

Comparison between Three Techniques for Determining Glomerular Filtration Rates: Tc-Diethylene Triamine Penta-Acetic Acid Renography, Double Plasma Sampling Method, and Single Plasma Sampling Method in Vietnamese Patients.

Unlabelled: Glomerular filtration rate (GFR) is an important indicator of renal function. Many methods have been developed to determine GFR in clinical examinations. This study aims to correlate between radionuclide plasma sampling methods (single and double blood samples, methods) and Gate's method using Tc-diethylene triamine penta-acetic acid (Tc-DTPA) renography.

Discovery of novel β-turn mimetic-based peptides as novel quorum sensing inhibitors of gram-negative bacteria.

To date, a very limited number of peptides reported as quorum sensing inhibitors. Herein, we report the synthesis and evaluation of a series of β-turn mimetic-based peptides as potent quorum sensing inhibitors and antibiofilm formation. In this series, peptides P1, P4, and P5 showed very promising anti-quorum sensing activity on lasB-gfp reporter strain of Pseudomonas aeruginosa without affecting bacterial growth.

Design, synthesis, and evaluation of novel -substituted-1-(4-chlorobenzyl)-1-indol-3-carbohydrazides as antitumor agents.

In continuity of our search for novel anticancer agents acting as procaspase activators, we have designed and synthesised two series of ()-'benzylidene-carbohydrazides () and -(2-oxoindolin-3-ylidene)carbohydrazides () incorporating 1-(4-chlorobenzyl)-1-indole core. Bioevaluation showed that the compounds, especially compounds in series , exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). Within series , compounds with 2-OH substituent () exhibited very strong cytotoxicity in three human cancer cell lines assayed with IC values in the range of 0.

Antimicrobial peptides - Advances in development of therapeutic applications.

The severe infection is becoming a significant health problem which threaten the lives of patients and the safety and economy of society. In the way of finding new strategy, antimicrobial peptides (AMPs) - an important part of host defense family, emerged with tremendous potential. Up to date, huge numbers of AMPs has been investigated from both natural and synthetic sources showing not only the ability to kill microbial pathogens but also propose other benefits such as wound healing, anti-tumor, immune modulation.

Design, synthesis and evaluation of novel indirubin-based N-hydroxybenzamides, N-hydroxypropenamides and N-hydroxyheptanamides as histone deacetylase inhibitors and antitumor agents.

Several novel indirubin-based N-hydroxybenzamides, N-hydropropenamides and N-hydroxyheptanamides (4a-h, 7a-h, 10a-h) were designed using a fragment-based approach with structural features extracted from several previously reported HDAC inhibitors, such as SAHA (vorinostat), MGCD0103 (mocetinostat), nexturastat A and PXD-101 (belinostat). The biological results reveal that our compounds showed excellent cytotoxicity toward three common human cancer cell lines (SW620, PC-3 and NCI-H23) with IC values ranging from 0.09 to 0.

The beneficial role of FeNO in association with GINA guidelines for titration of inhaled corticosteroids in adult asthma: A randomized study.

Purpose: This study aimed to demonstrate the role of fractional concentration of exhaled nitric oxide (FeNO) in association with Global Initiative for Asthma (GINA) guidelines for treatment of adult patients with asthma.

Methods: It was a prospective and randomized study. The symptomatic asthmatic patients were randomly divided into two groups: GINA group (followed GINA guidelines; N = 86) or GINA + FeNO group (followed GINA guidelines + FeNO for titration of inhaled corticosteroids - ICS; N = 90).

LEGO-Inspired Drug Design: Unveiling a Class of Benzo[d]thiazoles Containing a 3,4-Dihydroxyphenyl Moiety as Plasma Membrane H -ATPase Inhibitors.

The fungal plasma membrane H -ATPase (Pma1p) is a potential target for the discovery of new antifungal agents. Surprisingly, no structure-activity relationship studies for small molecules targeting Pma1p have been reported. Herein, we disclose a LEGO-inspired fragment assembly strategy for the design, synthesis, and discovery of benzo[d]thiazoles containing a 3,4-dihydroxyphenyl moiety as potential Pma1p inhibitors.

Difluoroacetic Acid as a New Reagent for Direct C-H Difluoromethylation of Heteroaromatic Compounds.

A technically simple procedure for direct C-H difluoromethylation of heteroaromatic compounds using off-the-shelf difluoroacetic acid as the difluoromethylating reagent has been developed. Mono-difluoromethylation versus bis-difluoromethylation is controlled as the result of the reaction temperature. The reactions described here enable access to the late-stage C-H mono- and bis-difluoromethylation for preparation of tool compounds for chemical biology and provide access to this hitherto untapped substituent for drug discovery.

Metformin, an Anthropogenic Contaminant of Seidlitzia rosmarinus Collected in a Desert Region near the Gulf of Aqaba, Sinai Peninsula.

A phytochemical investigation of Seidlitzia rosmarinus collected along the shoreline of the Gulf of Aqaba in the remote southern desert region of the Sinai peninsula has revealed the presence of the registered drug metformin (4). However, analysis of the C content revealed the drug to be an anthropogenic contaminant. Consequently, natural product researchers should be aware that compounds isolated from plants might originate from environmental contamination rather than biosynthesis.

Fusaric acid and analogues as Gram-negative bacterial quorum sensing inhibitors.

Taking advantage of microwave-assisted synthesis, efficient and expedite procedures for preparation of a library of fusaric acid and 39 analogues are reported. The fusaric acid analogues were tested in cell-based screening assays for inhibition of the las and rhl quorum sensing system in Pseudomonas aeruginosa and the lux quorum sensing system in Vibrio fischeri. Eight of the 40 compounds in the library including fusaric acid inhibited lux quorum sensing and one compound inhibited activity of the las quorum sensing system.

Demethoxycurcumin Is A Potent Inhibitor of P-Type ATPases from Diverse Kingdoms of Life.

P-type ATPases catalyze the active transport of cations and phospholipids across biological membranes. Members of this large family are involved in a range of fundamental cellular processes. To date, a substantial number of P-type ATPase inhibitors have been characterized, some of which are used as drugs.

Privileged substructure-based diversity-oriented synthesis pathway for diverse pyrimidine-embedded polyheterocycles.

A new diversity-oriented synthesis pathway for the fabrication of a pyrimidine-embedded polyheterocycles library was developed for potential interactions with diverse biopolymers. Five different pyrimidine-embedded core skeletons were synthesized from ortho-alkynylpyrimidine carbaldehydes by a silver- or iodine-mediated tandem cyclization strategy. The resulting polyheterocycles possess diverse fused ring sizes and positions with potential functionalities for further modification.

New benzothiazole/thiazole-containing hydroxamic acids as potent histone deacetylase inhibitors and antitumor agents.

Results from clinical studies have demonstrated that inhibitors of histone deacetylase (HDAC) enzymes possess promise for the treatment of several types of cancer. Zolinza(®) (widely known as SAHA) has been approved by the FDA for the treatment of T-cell lymphoma. As a continuity of our ongoing research to find novel small molecules to target these important enzymes, we synthesized a series of benzothiazole-containing analogues of SAHA and found several compounds with very potent anticancer cytotoxicity.