Design and synthesis of 4-[4-formyl-3-(2-naphthyl)pyrazol-1-yl]benzoic acid derivatives as potent growth inhibitors of drug-resistant Staphylococcus aureus.

We report the synthesis and antimicrobial studies of a new series of naphthyl-substituted pyrazole-derived hydrazones. Many of these novel compounds are potent growth inhibitors of several strains of drug-resistant bacteria. These potent compounds have inclined growth inhibitory properties for planktonic Staphylococcus aureus and Acinetobacter baumannii, and its drug-resistant variants with minimum inhibitory concentration (MIC) as low as 0.78 and 1.56 µg ml-1, respectively. These compounds also show potent activity against S. aureus and A. baumannii biofilm formation and eradication properties. Time Kill Assay shows that these compounds are bactericidal for S. aureus and bacteriostatic for A. baumannii. The probable mode of action is the disruption of the bacterial cell membrane. Furthermore, potent compounds are nontoxic to human cell lines at several fold higher concentrations than the MICs.

Synthesis and Antimicrobial Studies of Coumarin-Substituted Pyrazole Derivatives as Potent Anti-Staphylococcus aureus Agents.

In this paper, synthesis and antimicrobial studies of 31 novel coumarin-substituted pyrazole derivatives are reported. Some of these compounds have shown potent activity against methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) as low as 3.125 µg/mL. These molecules are equally potent at inhibiting the development of MRSA biofilm and the destruction of preformed biofilm. These results are very significant as MRSA strains have emerged as one of the most menacing pathogens of humans and this bacterium is bypassing HIV in terms of fatality rate.

Synthesis and Antimicrobial Studies of 4-[3-(3-Fluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic Acid and 4-[3-(4-Fluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic Acid as Potent Growth Inhibitors of Drug-Resistant Bacteria.

Microbial resistance to antibiotics is an urgent and worldwide concern. Several pyrazole-derived hydrazones were synthesized by using benign reaction conditions. Several of these molecules are potent growth inhibitors of drug-resistant strains of Staphylococcus aureus and Acinetobacter baumannii with minimum inhibitory concentration values as low as 0.39 µg/mL. Furthermore, these molecules are nontoxic to human cells at high concentrations. Some of these molecules were tested for their ability to disrupt the bacterial membrane by using the SYTO-9/propidium iodide (BacLight) assay.

Synthesis of Hydrazone Derivatives of 4-[4-Formyl-3-(2-oxochromen-3-yl)pyrazol-1-yl]benzoic acid as Potent Growth Inhibitors of Antibiotic-resistant Staphylococcus aureus and Acinetobacter baumannii.

Microbial resistance to drugs is an unresolved global concern, which is present in every country. Developing new antibiotics is one of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat bacterial resistance to drugs. Based on our lead molecules, we report the synthesis and antimicrobial studies of 27 new pyrazole derivatives. These new coumarin-pyrazole-hydrazone hybrids are readily synthesized from commercially available starting materials and reagents using benign reaction conditions. All the synthesized molecules were tested against 14 Gram-positive and Gram-negative bacterial strains. Several of these molecules have been found to be potent growth inhibitors of several strains of these tested bacteria with minimum inhibitory concentrations as low as 1.56 µg/mL. Furthermore, active molecules are non-toxic in in vitro and in vivo toxicity studies.

Benign Synthesis of Thiazolo-androstenone Derivatives as Potent Anticancer Agents.

An unprecedented reaction of thiourea derivatives with 6ß-bromoandrostenedione has been discovered for the formation of aminothiazolo-androstenones via a simple, safer, cascade protocol that enables the syntheses of novel molecules by using readily available reagents. The reaction mechanism of product formation has been rationalized by density functional theory calculations. This benign methodology accentuates a domino protocol deploying a renewable solvent, ethanol, while generating novel compounds that display potent growth inhibitory effects in in vitro studies for several cancer cell lines at submicromolar concentrations.

Hexafluoroisopropanol-Mediated Domino Reaction for the Synthesis of Thiazolo-androstenones: Potent Anticancer Agents.

A cascade reaction of thioamides with 6ß-bromoandrostenedione in hexafluoroisopropanol formed substituted thiazolo-androstenones. This is a simple and mild protocol to synthesize novel molecules by using readily available reagents and substrates. Feasibility of the reaction has been rationalized by density functional theory calculations. Moreover, these compounds are potent growth inhibitors of colon, central nervous system, melanoma, ovarian, and renal cancer cell lines with 50% growth inhibition values as low as 1.04 µM.