Exploration of the Topical Nanoemulgel Bearing with Ferulic Acid and Essential Oil for Diabetic Wound Healing.

To investigate the anti-inflammatory, antioxidant, and diabetic wound healing properties of the novel topical formulation [Ferulic acid-loaded nanoemulgel (DLMGO-G)]. Ferulic acid nanoemulsion developed with lemongrass oil is investigated in diabetic wound healing. Further nanoemulsion is incorporated into 1% carbopol 934 to obtain the DLMGO-G.

Pharmacological Evaluation of Bakuchiol From Psoralea corylifolia L. as Potent Antimicrobial Agent Against Staphylococcus aureus.

The surge in multidrug resistance in Staphylococcus aureus is the pressing need to identify novel alternatives to combat antimicrobial resistance effectively. Bakuchiol is a bioactive prenylated phenolic meroterpene largely abundant in the seeds of Psoralea corylifolia. In this study, we present the biological assessment of bakuchiol derived from P.

Thymoquinone loaded nanoemulgel in streptozotocin induced diabetic wound.

To treat diabetic wound healing with a novel Thymoquinone (TQ) loaded nanoformulation by using combination of essentials oils. TQ nanoemulsion (NE) was developed with seabuckthorn & lavender essential oils by phase inversion method and mixture design. Further, DIAGEL is obtained by incorporating NE into 1% carbopol934.

Advancements and challenges in tuberculosis drug discovery: A comprehensive overview.

Tuberculosis continues to pose a health challenge causing the loss of millions of lives despite the existence of multiple drugs, for treatment. The emergence of drug-resistant strains has made the situation more complex making it increasingly difficult to fight against this disease. This review outlines the challenges associated with TB drug discovery, the nature of Mycobacterium tuberculosis shedding light on the mechanisms that lead to treatment failure and antibiotic resistance.

Design, synthesis, and biological evaluation of pyrazole-ciprofloxacin hybrids as antibacterial and antibiofilm agents against .

In our continued efforts to tackle antibiotic resistance, a new series of pyrazole-ciprofloxacin hybrids were designed, synthesized, and evaluated for their antibacterial activity against (), (), and (). Most of the compounds exhibited good to excellent activities against , and six compounds (7a, 7b, 7d, 7g, 7k, and 7p) exhibited higher or comparable activity (MIC = 0.125-0.

2-Aryl-Benzoimidazoles as Type II NADH Dehydrogenase Inhibitors of .

The nonproton pumping type II NADH dehydrogenase in is essential for meeting the energy needs in terms of ATP under normal aerobic and stressful hypoxic environmental states. Type II NADH dehydrogenase conduits electrons into the electron transport chain in , which results in ATP synthesis. Therefore, the inhibition of NDH-2 ensures the abolishment of the entire ATP synthesis machinery.

Design, Synthesis, Evaluation of Antitubercular Activity and Insilco Studies of Novel 1,5-Naphthyridin-2(1H)-One Pendent 1,2,3-Triazoles.

A library of 1,5-Naphthyridin-2(1H)-one based 1,2,3-triazole analogues (11a-q) were synthesized via series of reactions such as protection, oxidation, cyclization and click chemistry. The new molecules were tested for their antitubercular activity against M. tuberculosis mc6230 and determined the minimum inhibitory concentration (MIC) employing Rifampicin as reference.

Development and Evaluation of Bis-benzothiazoles as a New Class of Benzothiazoles Targeting DprE1 as Antitubercular Agents.

Benzothiazole-bearing compounds have emerged as potential noncovalent DprE1 (decaprenylphosphoryl-β-d-ribose-2'-epimerase) inhibitors active against . Based on structure-based virtual screening (PDB ID: 4KW5), a focused library of thirty-one skeletally diverse benzothiazole amides was prepared, and the compounds were assessed for their antitubercular activity against H37Ra. Most potent compounds and were further evaluated against the H37Rv strain by the microdilution assay method.

Facile one-pot synthesis of N-pyridinylaminonaphthol derivatives and their antibacterial evaluation against multidrug-resistant Staphylococcus aureus.

The escalating severity of the menace posed by bacterial resistance has rendered the existing antibiotics less effective, thus necessitating the discovery of new antibacterial agents. The current study reports the exploration of substituted N-pyridinylaminonaphthols produced by a straightforward, one-pot multicomponent reaction process as antibacterial agents. The synthesized derivatives were assessed in vitro for their antibacterial properties against a panel of bacterial pathogens.

P-glycoprotein inhibitors as an adjunct therapy for TB.

The primary challenge in TB treatment is the emergence of multidrug-resistant TB (MDR-TB). One of the major factors responsible for MDR is the upregulation of efflux pumps. Permeation-glycoprotein (P-gp), an efflux pump, hinders the bioavailability of the administered drugs inside the infected cells.

Antitubercular activity of 2-mercaptobenzothiazole derivatives targeting type II NADH dehydrogenase.

() type II NADH dehydrogenase (NDH-2) transports electrons into the mycobacterial respiratory pathway at the cost of reduction of NADH to NAD and is an attractive drug target. Herein, we have synthesised a series of 2-mercaptobenzothiazoles (C1-C14) and evaluated their anti-tubercular potential as NDH-2 inhibitors. The synthesised compounds C1-C14 were evaluated for MIC and ATP depletion against H37Ra, , and H37Rv mc 6230.

Cytochrome oxidase: an emerging anti-tubercular drug target.

Cytochrome (cyt-) oxidase, one of the two terminal oxidases in the () oxidative phosphorylation pathway, plays an indispensable role in maintaining the functionality of the metabolic pathway under stressful conditions. However, the absence of this oxidase in eukaryotic cells allows researchers to select it as a potential drug target for the synthesis of anti-tubercular (anti-TB) molecules. Cyt- inhibitors have often been combined with cytochrome / super-complex inhibitors in anti-TB drug regimens to achieve a desired bactericidal response.

Exploring rhodanine linked enamine-carbohydrazide derivatives as mycobacterial carbonic anhydrase inhibitors: Design, synthesis, biological evaluation, and molecular docking studies.

With the rise of multidrug-resistant tuberculosis, the imperative for an alternative and superior treatment regimen, incorporating novel mechanisms of action, has become crucial. In pursuit of this goal, we have developed and synthesized a new series of rhodanine-linked enamine-carbohydrazide derivatives, exploring their potential as inhibitors of mycobacterial carbonic anhydrase. The findings reveal their efficacy, displaying notable selectivity toward the mycobacterial carbonic anhydrase 2 (mtCA 2) enzyme.

Multifunctional Wound Curation Dressing Material FemuFrost─An Antioxidant-Loaded Nanoemulsion Frosted Patch of Poly(vinyl alcohol) and Hyaluronic Acid.

The wound curation dressing material should own explicit elements to aggrandize wound cessation. The cryogel of poly(vinyl alcohol) (PVA) and hyaluronic acid (HA) is deemed to promote the angiogenesis, production of extracellular matrix components, granulation, and epithelialization. The research aims to tailor and evaluate the composite PVA/HA cryogel ingrained ferulic acid-loaded nanoemulsion patch labeled as PH-FemuFrost to improve the therapeutic properties and mechanical strength of the patches.

A comprehensive review of genomics, transcriptomics, proteomics, and metabolomic insights into the differentiation of Pseudomonas aeruginosa from the planktonic to biofilm state: A multi-omics approach.

Biofilm formation by Pseudomonas aeruginosa is primarily responsible for chronic wound and lung infections in humans. These infections are persistent owing to the biofilm's high tolerance to antimicrobials and constantly changing environmental factors. Understanding the mechanism governing biofilm formation can help to develop therapeutics explicitly directed against the molecular markers responsible for this process.

GaMF1.39's antibiotic efficacy and its enhanced antitubercular activity in combination with clofazimine, Telacebec, ND-011992, or TBAJ-876.

New drugs are needed to combat multidrug-resistant tuberculosis. The electron transport chain (ETC) maintains the electrochemical potential across the cytoplasmic membrane and allows the production of ATP, the energy currency of any living cell. The mycobacterial engine F-ATP synthase catalyzes the formation of ATP and has come into focus as an attractive and rich drug target.

Exploring and exploiting the host cell autophagy during Mycobacterium tuberculosis infection.

Tuberculosis, caused by Mycobacterium tuberculosis, is a fatal infectious disease that prevails to be the second leading cause of death from a single infectious agent despite the availability of multiple drugs for treatment. The current treatment regimen involves the combination of several drugs for 6 months that remain ineffective in completely eradicating the infection because of several drawbacks, such as the long duration of treatment and the side effects of drugs causing non-adherence of patients to the treatment regimen. Autophagy is an intracellular degradative process that eliminates pathogens at the early stages of infection.

Exploration of 3-aryl pyrazole-tethered sulfamoyl carboxamides as carbonic anhydrase inhibitors.

Herein, we report the design and synthesis of two series of pyrazole-tethered sulfamoyl phenyl acetamides and pyrazole-tethered sulfamoyl phenyl benzamides. The synthesized compounds were investigated for inhibiting two human carbonic anhydrases, human carbonic anhydrases (hCA) I and II, and those of the bacterial pathogen Mycobacterium tuberculosis, mtCA 1-3. The results indicate that, among the synthesized compounds, pyrazoles with 4-aminobenzene sulfonamide were more selective toward hCA I and II over mtCAs, and compounds with 3-aminobenzene sulfonamide were selective toward mtCA 1-3 over hCA I, II.

Synthesis and pharmacological evaluation of 1,3-diaryl substituted pyrazole based (thio)urea derivatives as potent antimicrobial agents against multi-drug resistant and .

The urgent development of newer alternatives has been deemed a panacea for tackling emerging antimicrobial resistance effectively. Herein, we report the design, synthesis, and biological evaluation of 1,3-diaryl substituted pyrazole-based urea and thiourea derivatives as antimicrobial agents. Preliminary screening results revealed that compound 7a (3,4-dichlorophenyl derivative) exhibited potent activity against (MIC = 0.

Unravelling the flexibility of an escape way for the bacilli.

The persistence of makes it difficult to eradicate the associated infection from the host. The flexible nature of mycobacteria and their ability to adapt to adverse host conditions give rise to different drug-tolerant phenotypes. Granuloma formation restricts nutrient supply, limits oxygen availability and exposes bacteria to a low pH environment, resulting in non-replicating bacteria.

M. tuberculosis relies on trace oxygen to maintain energy homeostasis and survive in hypoxic environments.

The bioenergetic mechanisms by which Mycobacterium tuberculosis survives hypoxia are poorly understood. Current models assume that the bacterium shifts to an alternate electron acceptor or fermentation to maintain membrane potential and ATP synthesis. Counterintuitively, we find here that oxygen itself is the principal terminal electron acceptor during hypoxic dormancy.

Role of transcription termination factor Rho in anti-tuberculosis drug discovery.

Mycobacterial infections, including multidrug and extreme drug-resistant (MDR and XDR) infections, are a severe challenge and create a virtual antibiotic-deficient era. Bacterial transcription is an established antimicrobial drug target. In mycobacteria, efficient transcription termination relies on the ATP-dependent RNA helicase factor Rho.

Turbidity-Based MIC Assay and Characterization of Spontaneous Drug Resistant Mutants in Mycobacterium ulcerans.

Generation and characterization of drug resistant mutants is a powerful tool in antimicrobial drug discovery for identification of the molecular target of an investigational drug candidate. The method is relatively simple to be conducted in a classical microbiology laboratory. Its value has been augmented by the employment of next generation sequencing techniques to characterize single-nucleotide polymorphisms associated with drug resistance.