Efficient Antibacterial Agents Research Articles

SYNTHESIS, REACTIONS AND BIOLOGICAL ACTIVITY OF PHOSPHORUS-CONTAINING DERIVATIVES OF CHROMONE AND COUMARIN

Chromone and coumarin derivatives exhibit a wide spectrum of biological activity, including spasmolytic, antiarrhythmic, cardiothonic, antiviral, and anticancer properties. Phosphorus-containing chromone and coumarin derivatives form a novel group of compounds, possessing remarkable cytotoxicity and alkylating and anticancer activity against selected tumor cell lines. Derivatives containing a phosphorus atom at position 2 of a γ-pyrone ring are known to be efficient antibacterial agents. This review presents methods developed for the synthesis of derivatives of chromone and coumarin that contain a phosphonate moiety. Among them, the reaction of derivatives of 2-hydroxyacetophenone with phosphonic compounds is the one most frequently used. Some analogues were characterized by X-ray crystallography.

Learning from nature's drug factories: nonribosomal synthesis of macrocyclic peptides.

With the discovery of penicillin as an efficient antibacterial agent isolated from the fungus Penicillium notatum , microorganisms attracted considerable attention as a new source for pharmaceutical agents. Screening of microbial extracts revealed the large structural diversity of natural compounds

Synthesis and Antibacterial Activity of Fused Mannich Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and antibacterial activity of fused Mannich ketones

New Mannich ketones of fused bicyclic ketones as 1-indanones and 1-tetralones were prepared using the classical acid-catalysed Mannich reaction. Known members of this family were used in comparative biological tests. Antibacterial activity of these new water-soluble compounds was reported against Pseudomonas aeruginosa, Escherichia coli, E. coli ReD31m4, Salmonella minnesota Re595, Shigella sonnei Re4350, Staphylococcus aureus, Staphylococcus saprophyticus, Micrococcus luteus and Bacillus subtilis standard strains. Human cytotoxicity of our new compounds was evaluated against HeLa cell line. Some compounds showed low cytotoxicity (56.738 nM mL −1 for 24, 47.497 nM mL −1 for 31 and 48.379 nM mL −1 for 26) and proved to be efficient antibacterial agents against the Gram-positive and partly against E. coli strains. Minimum inhibitory concentrations (MIC) changed in the range of 1.56–>200 μg mL −1. The deep rough mutants showed (generally eight times) higher sensitivity toward the compounds than the smooth E. coli. Hence, the permeability of Gram-negative outer membrane can influence the MIC values of our compounds. A preliminary quantitative structure–activity relationship (QSAR) study indicated the maximum positive charge (MaxQ +) as the parameter that most significantly affected antibacterial activity against E. coli. In B. subtilis, the influence of a topological descriptor (first-order valence-connectivity index, XV1) was also revealed; however, other strains did not yield meaningful QSAR with the set of descriptors employed.

Synthesis and antibacterial study of unsaturated Mannich ketones

Several Mannich ketones of 2-arylmethylenecycloalkanones were synthesised using the classical acid-catalysed Mannich reaction. Antibacterial activity of these new water-soluble compounds was reported against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Staphylococcus saprophyticus, Micrococcus luteus and Bacillus subtilis standard strains. Human cell line cytotoxicity of our new compounds was evaluated against HeLa cell lines. Some compounds showed low cytotoxicity (41.52 nM mL −1 for 14 and 46.60 nM mL −1 for 18) and proved to be efficient antibacterial agents against the Gram-positive strains. Minimum inhibitory concentrations varied from 1.56 to 100 μg mL −1. The mechanism of action was examined, too.

Resistance to trimethoprim and sulfonamides.

Sulfonamides and trimethoprim have been used for many decades as efficient and inexpensive antibacterial agents for animals and man. Resistance to both has, however, spread extensively and rapidly. This is mainly due to the horizontal spread of resistance genes, expressing drug-insensitive variants of the target enzymes dihydropteroate synthase and dihydrofolate reductase, for sulfonamide and trimethoprim, respectively. Two genes, sul1 and sul2, mediated by transposons and plasmids, and expressing dihydropteroate synthases highly resistant to sulfonamide, have been found. For trimethoprim, almost twenty phylogenetically different resistance genes, expressing druginsensitive dihydrofolate reductases have been characterized. They are efficiently spread as cassettes in integrons, and on transposons and plasmids. One particular gene, dfr9, seems to have originally been selected in the intestine of swine, where it was found in Escherichia coli, on large plasmids in a disabled transposon, Tn5393, originally found in the plant pathogen Erwinia amylovora. There are also many examples of chromosomal resistance to sulfonamides and trimethoprim, with different degrees of complexity, from simple base changes in the target genes to transformational and recombinational exchanges of whole genes or parts of genes, forming mosaic gene patterns. Furthermore, the trade-off, seen in laboratory experiments selecting resistance mutants, showing drug-resistant but also less efficient (increased Kms) target enzymes, seems to be adjusted for by compensatory mutations in clinically isolated drug-resistant pathogens. This means that susceptibility will not return after suspending the use of sulfonamide and trimethoprim.

Synthesis of Phenyl-1,3-thiazole Substituted Amino s-triazines as Antibacterial Agents

Amino s-triazines are widely believed to exert their antibacterial effects by nonspecific mechanisms. We assessed the extent to which physicochemical properties can be exploited to promote discriminative activity. In a wide search program towards new and efficient antibacterial agents, a series of amino substituted s-triazines were synthesized and subsequently screened for their in-vitro antibacterial activity against three Gram positive (Bacillus subtilis, B. cereus, Staphylococcus aureus) and three Gram-negative microorganism (Salmonella typhi, Escherichia coli, Klebsiella aerogenes) by the broth dilution technique, recommended by European Committee for antimicrobial susceptibility testing (EUCAST) with reference to streptomycin. The phenyl-1,3-thiazole substituted amino-s-triazine derivatives showed good antibacterial activity. Key words: Antibacterial activity, Bacterial resistance, Broth dilution technique, Physicochemical properties, s-Triazine. doi: 10.3329/dujps.v7i2.2164 Dhaka Univ. J. Pharm. Sci. 7(2): 107-111, 2008 (December)

Transcutaneous absorption of boric acid

Summary 1. Three case of transcutaneous absorption of boric acid in infants treated for diaper rash are reported. One child died. The diagnoses were made on clinical grounds and corroborated by laboratory analysis of blood, urine, and cerebrospinal fluid. 2. Borated dusting powders, widely sold commercially, are shown to be capable of forming saturated solutions in common clinical situations with possible resultant absorption of toxic quantities through broken skin. 3. The use of boric acid should be discontinued in favor of safe and efficient antibacterial agents that are now available.