Comprehensive biological evaluation of Rheinal as a potent antimicrobial, alone and in combination with gentamicin and minocycline targeting MDR S. aureus in vitro and in vivo.

Antimicrobial resistance is recognized as a threat to healthcare systems worldwide and consequently, discovery and development of new antimicrobials is a top priority. Natural products and their derivatives have historically been an excellent source of antimicrobials. In this context, anti-bacterial activity of synthesized natural product derivative, Rheinal, was assessed against a panel of Gram-positive and Gram-negative bacterial pathogens where it exhibited potent bactericidal activity against S.

Linear Antimicrobial Peptide, Containing a Diindolyl Methane Unnatural Amino Acid, Potentiates Gentamicin Against Methicillin-Resistant Staphylococcus aureus.

The headway for the management of emerging resistant microbial strains has become a demanding task. Over the years, antimicrobial peptides (AMP), have been recognized and explored for their highly systematized SAR and antibacterial properties. With this background, we have reported a new class of AMPs.

Membrane-targeting, ultrashort lipopeptide acts as an antibiotic adjuvant and sensitizes MDR gram-negative pathogens toward narrow-spectrum antibiotics.

Globally, infections due to multi-drug resistant (MDR) Gram-negative bacterial (GNB) pathogens are on the rise, negatively impacting morbidity and mortality, necessitating urgent treatment alternatives. Herein, we report a detailed bio-evaluation of an ultrashort, cationic lipopeptide 'SVAP9I' that demonstrated potent antibiotic activity and acted as an adjuvant to potentiate existing antibiotic classes towards GNBs. Newly synthesized lipopeptides were screened against ESKAPE pathogens and cytotoxicity assays were performed to evaluate the selectivity index (SI).

Naturally Derived Malabaricone B as a Promising Bactericidal Candidate Targeting Multidrug-Resistant also Possess Synergistic Interactions with Clinical Antibiotics.

The emergence of multidrug-resistant (MDR) superbugs underlines the urgent need for innovative treatment options to tackle resistant bacterial infections. The clinical efficacy of natural products directed our efforts towards developing new antibacterial leads from naturally abundant known chemical structures. The present study aimed to explore an unusual class of phenylacylphenols (malabaricones) from as antibacterial agents.

Oxiconazole Potentiates Gentamicin against Gentamicin-Resistant Staphylococcus aureus and .

Amid the mounting burden of multidrug-resistant (MDR) bacterial infections on health care worldwide, drug repurposing, a time and cost-effective strategy to identify new applications for drugs approved for other indications, can effectively fill the void in the current antibiotic pipeline. In this study, we have repurposed a topical antifungal agent, oxiconazole, in combination with gentamicin against skin infections caused by multidrug-resistant Staphylococcus aureus. Oxiconazole was identified as having antibacterial activity against S.

Characterization and antimicrobial evaluation of anthraquinones and triterpenes from .

Chemical investigation of roots of the plant, Linn, led to the isolation of an undescribed anthraquinone, cordifoquinone R, determined as 1,2-dihydroxy-6-methoxyanthracene-9,10-dione ( based on the 1D and 2D NMR analyses and HRESIMS. Ten other known compounds 1,4-dihydroxy-2-methoxyanthracene-9,10-dione (), rubiadin (), xanthopurpurin (), 1-methoxy-3-hydroxy-2-carbomethoxy-9,10-anthraquinone (), alizarin (), β-sitosterol glucoside (), scopoletin (), oleanolic acid, (), pomolic acid (), queretaroic acid () were also isolated. Out of these compounds, , , and are first reported from this plant species.

Heterocyclic Diaryliodonium-Based Inhibitors of Carbapenem-Resistant Acinetobacter baumannii.

Finding new therapeutic strategies against Gram-negative pathogens such as Acinetobacter baumannii is challenging. Starting from diphenyleneiodonium (dPI) salts, which are moderate Gram-positive antibacterials, we synthesized a focused heterocyclic library and found a potent inhibitor of patient-derived multidrug-resistant Acinetobacter baumannii strains that significantly reduced bacterial burden in an animal model of infection caused by carbapenem-resistant Acinetobacter baumannii (CRAB), listed as a priority 1 critical pathogen by the World Health Organization. Next, using advanced chemoproteomics platforms and activity-based protein profiling (ABPP), we identified and biochemically validated betaine aldehyde dehydrogenase (BetB), an enzyme that is involved in the metabolism and maintenance of osmolarity, as a potential target for this compound.

Antimicrobial efficacy of a hemilabile Pt(II)-NHC compound against drug-resistant and .

Three platinum(II)-N-heterocyclic carbene (NHC) compounds [Pt(L)Cl](PF) (1), [Pt(L)(COD)](PF) (2) and [Pt(L)Cl] (3) were synthesized bearing pyridyl-functionalized butenyl-tethered (LH) and -butyl tethered (LH) NHC ligands, and their antibacterial activity against clinically relevant human pathogens was evaluated. Complex 1 was designed to have one of its metal coordination sites masked with a hemilabile butenyl group. The antibacterial activity spectrum against the ESKAPE panel of pathogens shows superior activity of 1 compared to 2 and 3 against the Gram-positive pathogen.

Pyrvinium pamoate potentiates levofloxacin against levofloxacin-resistant .

Drug repurposing is a viable approach to expediting the tedious conventional drug discovery process, given rapidly increasing bacterial resistance. In this context, we have repurposed pyrvinium pamoate (PP) for its antibacterial activity against . US FDA-approved non-antibiotics were screened against clinically relevant bacterial pathogens to identify antibacterials.

Developing the Natural Prenylflavone Artocarpin from as a Potential Lead Targeting Pathogenic, Multidrug-Resistant , Persisters and Biofilms with No Detectable Resistance.

The genus , a nutraceutical, is widely used in traditional medicine for treatment of many chronic diseases including infections. Lam., an evergreen tree endogenous to the Western Ghats of India, is a well-documented medicinal plant in Hortus Malabaricus, the oldest comprehensive printed book on the natural plant wealth of Asia.

Nitazoxanide potentiates linezolid against linezolid-resistant Staphylococcus aureus in vitro and in vivo.

Background: Antimicrobial resistance is a growing menace, claiming millions of lives all over the world. In this context, drug repurposing is one approach gaining interest as a suitable alternative to conventional drug discovery and development.

Methods: Whole-cell assays were used to screen FDA-approved drugs to identify novel antimicrobial agents active against bacterial pathogens.

Cudraflavone C from as a Promising Inhibitor of Pathogenic, Multidrug-Resistant , Persisters, and Biofilms: A New Insight into a Rational Explanation of Traditional Wisdom.

Lam., or wild jack, a perennial tree of the Western Ghats of peninsular India, serves as a rich source of flavonoids. The indigenous knowledge of this multipurpose flora chronicles the efficient property of its bark as a natural treatment for various skin infections.

Synthesis and structure-activity relationship of new chalcone linked 5-phenyl-3-isoxazolecarboxylic acid methyl esters potentially active against drug resistant Mycobacterium tuberculosis.

In search of novel therapeutic agents active against emerging drug-resistant Mycobacterium tuberculosis and to counter the long treatment protocol of existing drugs, herein we present synthesis and biological evaluation of a new series of 5-phenyl-3-isoxazolecarboxylic acid methyl ester-chalcone hybrids. Among 35 synthesized compounds, 32 analogues displayed potent in-vitro activity against Mycobacterium tuberculosis H37Rv with MIC 0.12-16 μg/mL.

Design, synthesis, in silico, and in vitro evaluation of 3-phenylpyrazole acetamide derivatives as antimycobacterial agents.

Mycobacterium tuberculosis (Mtb) is one of the most dangerous pathogens affecting immunocompetent and immunocompromised patients worldwide. Novel molecules, which are efficient and can reduce the duration of therapy against drug-resistant strains, are an urgent unmet need of the hour. In our current study, a series of new 2-(3-phenyl-1H-pyrazol-1-yl)acetamide and N'-benzylidene-2-(3-phenyl-1H-pyrazol-1-yl)acetohydrazide derivatives were designed, synthesized, and evaluated for their antimycobacterial potential.

Copper mediated one-pot synthesis of quinazolinones and exploration of piperazine linked quinazoline derivatives as anti-mycobacterial agents.

A facile method was developed for the synthesis of quinazolinone derivatives in a one-pot condensation reaction amine generation using ammonia as the amine source and with the formation of four new C-N bonds in good to excellent yields. With the optimised method, we synthesized a library of piperazine linked quinazoline derivatives and the synthesized compounds were evaluated for their inhibitory activity against . The compounds 8b, 8e, 8f, 8m, 8n and 8v showed potent anti-mycobacterial activity with MIC values of 2-16 μg mL.

Synthesis and evaluation of new quinazoline-benzimidazole hybrids as potent anti-microbial agents against multidrug resistant Staphylococcus aureus and Mycobacterium tuberculosis.

Owing to the rapid rise in antibiotic resistance, infectious diseases have become serious threat to public health. There is an urgent need to develop new antimicrobial agents with diverse chemical structures and novel mechanisms of action to overcome the resistance. In recent years, Quinazoline-benzimidazole hybrids have emerged as a new class of antimicrobial agents active against S.

Peptide Nanostructure-Mediated Antibiotic Delivery by Exploiting HS-Rich Environment in Clinically Relevant Bacterial Cultures.

Stimuli-responsive self-destructing soft structures serve as versatile hosts for the encapsulation of guest molecules. A new paradigm for HS-responsive structures, based on a modified tripeptide construct, is presented along with microscopy evidence of its time-dependent rupture. As a medicinally interesting application, we employed these commercial antibiotic-loaded soft structures for successful drug release and inhibition of clinically relevant, drug-susceptible, and methicillin-resistant .

Synthesis of novel 4,5-dihydropyrrolo[1,2-a]quinoxalines, pyrrolo[1,2-a]quinoxalin]-2-ones and their antituberculosis and anticancer activity.

A facile strategy was developed for the synthesis of biologically important 4,5-dihydropyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a]quinoxalin]-2-ones by treating 2-(1H-pyrrol-1-yl)anilines with imidazo[1,2-a]pyridine-3-carbaldehyde or isatin, using amidosulfonic acid (NH SO ) as a solid catalyst in water at room temperature. The protocol has been extended to electrophile ninhydrin. The catalyst could be recycled for six times without the loss of activity.

Vancomycin Derivative Inactivates Carbapenem-Resistant and Induces Autophagy.

Vancomycin is a standard drug for the treatment of multidrug-resistant Gram-positive bacterial infections. Albeit, development of resistance (VRE, VRSA) and its inefficacy against persistent infections is a demerit. It is also intrinsically inactive against Gram-negative bacteria.

A novel molecular scaffold resensitizes multidrug-resistant S. aureus to fluoroquinolones.

Nosocomial infections arising from opportunistic pathogens, such as Staphylococcus aureus, are growing unabated, compounded by the rapid emergence of antimicrobial resistance. Herein, we demonstrate a new molecular design that exhibits excellent activity against multidrug-resistant S. aureus with no cytotoxicity and resensitizes fluoroquinolones (FQ) towards FQ-resistant methicillin-resistant S.

Rationally designed curcumin based ruthenium(ii) antimicrobials effective against drug-resistant Staphylococcus aureus.

Two new curcumin containing octahedral ruthenium(ii) polypyridyl complexes, viz. [Ru(NN)2(cur)](PF6) [NN = bpy (1), phen (2)], were designed to explore the antimicrobial activity against ESKAPE pathogens, especially with the Gram-positive drug resistant S. aureus.

Synthesis and biological evaluation of 2,4,5-trisubstituted thiazoles as antituberculosis agents effective against drug-resistant tuberculosis.

The dormant and resistant form of Mycobacterium tuberculosis presents a challenge in developing new anti-tubercular drugs. Herein, we report the synthesis and evaluation of trisubstituted thiazoles as antituberculosis agents. The SAR study has identified a requirement of hydrophobic substituent at C2, ester functionality at C4, and various groups with hydrogen bond acceptor character at C5 of thiazole scaffold.