Synthesis and antimicrobial activities of a novel series of heterocyclic α-aminophosphonates.

Two series of novel α-aminophosphonates having heterocyclic moieties were synthesized in high yields. The structures of the newly synthesized compounds were confirmed by their elemental analyses, IR, (1)H NMR and MS spectral data. These compounds were screened for their antibacterial activities against Escherichia coli (NCIM2065) as a Gram-negative bacterium, Bacillus subtilis (PC1219) and Staphylococcus aureus (ATCC25292) as Gram-positive bacteria, and Candida albicans and Saccharomyces cerevisiae as fungi.

Synthesis, antimicrobial and anticancer activities of a novel series of diphenyl 1-(pyridin-3-yl)ethylphosphonates.

A novel series of diphenyl 1-(arylamino)-1-(pyridin-3-yl)ethylphosphonates 1-5 was obtained in high yields from reactions of 3-acetyl pyridine with aromatic amines and triphenylphosphite in the presence of lithium perchlorate as a catalyst. The structures of the synthesized compounds were confirmed by IR, (1)H NMR spectral data and microanalyses. Compounds 1-5 showed high antimicrobial activities against Escherichia coli (NCIM2065) as a Gram-negative bacterium, Bacillus subtilis (PC1219) and Staphylococcus aureus (ATCC25292) as Gram-positive bacteria and Candidaalbicans and Saccharomyces cerevisiae as fungi, at low concentrations (10-100 μg/mL).

Studies on antiretroviral drug concentrations in breast milk: validation of a liquid chromatography-tandem mass spectrometric method for the determination of 7 anti-human immunodeficiency virus medications.

Studying the pharmacokinetics of antiretroviral drugs in breast milk has important implications for the health of both the mother and the infant, particularly in resource-poor countries. Breast milk is a highly complex biological matrix, yet it is necessary to develop and validate methods in this matrix, which simultaneously measure multiple analytes, as women may be taking any number of drug combinations to combat human immunodeficiency virus infection. Here, we report a novel extraction method coupled to high-performance liquid chromatography and tandem mass spectrometry for the accurate, precise, and specific measurement of 7 antiretroviral drugs currently prescribed to infected mothers.

Inhibition of mammalian aspartate transcarbamylase by quinazolinone derivatives.

Quinazolinone derivatives have been studied as both in vitro and in vivo inhibitors of aspartate transcarbamylase (ATCase). In vitro treatment of mammalian ATCase with four compounds revealed that they inhibited enzyme activity and that 2-phenyl-1,3-4(H)benzothiazin-4-thione was the most potent one. This compound acts as a noncompetitive inhibitor towards both aspartate and carbamoyl phosphate.

Development of a highly efficient extraction technique and specific multiplex assay for measuring antiretroviral drug concentrations in breast milk.

Understanding the pharmacology of drugs in breast milk is important for the health of both mother and baby. Current methods to measure drug concentrations in breast milk are not easily validated for precision or accuracy, primarily because of suboptimal sample clean-up. We report here an optimized clean-up method to remove both proteins and fat from milk, thereby enhancing the extraction efficiency of antiretroviral drugs.

Susceptibility of Biomphalaria alexandrina to the plant Azolla pinnata and some herbicides in relation to infection with Schistosoma mansoni miracidia.

Molluscicidal activity of the herebicides 2,4-D and Graminol, as well as both extracts and dry powder of the plant Azolla pinnata were evaluated against B. alexandrina snails. It was observed that 2,4-D proved to be the most toxic compound among he tested ones, showing LC90 of 52 ppm after 24 h of exposure.

Effect of the plant Azolla pinnata on survival, growth rate, fecundity and hatchability of egg-masses of Biomphalaria alexandrina snails.

Data indicated that Azolla pinnata plants variously reduce the growth rate of Biomphalaria alexandrina snails expressed as net increase in shell diameter (direct or indirect exposure). The plant density played an important role in this respect. The higher the plant density was the lower the growth rate and vice versa.

Effect of X-ray on the snails of schistosomiasis in Egypt.

Biomphalaria alexandrina and Bulinus truncatus snails were exposed to sublethal doses 0.2, 3, 5, 10 and 20 rad of X-ray. The survival and reproductive rates of these snails were highly affected by these doses.

Lithiation of 2-Alkyl-3-amino- and 2-Alkyl-3-(methylamino)-4(3H)-quinazolinones(1).

3-Amino-2-methyl-4(3H)-quinazolinone has been doubly lithiated, on nitrogen and in the 2-methyl group, with n-butyllithium. The lithium reagent thus obtained reacts with a variety of electrophiles (D(2)O, benzophenone, cyclohexanone, cyclopentanone, acetophenone, benzaldehyde, tetraisopropylthiuram disulfide (TITD)) to give the corresponding 2-substituted derivatives in very good yields. Reactions of the dilithio reagent with 2 molar equiv of methyl iodide or phenyl isocyanate give disubstituted derivatives.

Lithiation of 3-(Acylamino)-2-unsubstituted-, 3-(Acylamino)-2-ethyl-, and 3-(Acylamino)-2-propyl-4(3H)-quinazolinones: Convenient Syntheses of More Complex Quinazolinones(1).

3-(Pivaloylamino)- and 3-(acetylamino)-4(3H)-quinazolinones react with alkyllithium reagents to give 1,2-addition products in very good yields. Lithiation takes place with LDA and is regioselective at position 2. The lithium reagents thus obtained react with a variety of electrophiles to give the corresponding substituted derivatives in very good yields.

Eukaryotic DNA topoisomerases mediated DNA cleavage induced by a new inhibitor: NSC 665517.

A compound with a novel structure, NSC 665517, was tested in the National Cancer Institute Preclinical Drug Discovery Screen. With the COMPARE algorithm, the pattern of differential cytotoxicity for NSC 665517 most closely resembled those of known topoisomerase II (top2) inhibitors. In vitro data showed that NSC 665517 induced DNA cleavage in the presence of top2 and topoisomerase I (top1) (at a higher concentration).