Novel Thiazole Derivatives of Medicinal Potential: Synthesis and Modeling

This paper reports on the synthesis of new thiazole derivatives that could be profitably exploited in medical treatment of tumors. Molecular electronic structures have been modeled within density function theory (DFT) framework. Reactivity indices obtained from the frontier orbital energies as well as electrostatic potential energy maps are discussed and correlated with the molecular structure. X-ray crystallographic data of one of the new compounds is measured and used to support and verify the theoretical results

Raising the Diversity of Ugi Reactions Through Selective Alkylations and Allylations of Ugi Adducts

We report here selective Tsuji-Trost type allylation of Ugi adducts using a strategy based on the enhanced nucleophilicity of amide dianions. Ugi adducts derived from aromatic aldehydes were easily allylated at their peptidyl position with allyl acetate in the presence of palladium catalysts. These substitutions were compared to more classical transition metal free allylations using allyl bromides

Insights into the role of natural products in the control of the honey bee gut parasite (Nosema spp.)

The honey bee is an important economic insect due to its role in pollinating many agricultural plants. Unfortunately, bees are susceptible to many pathogens, including pests, parasites, bacteria, and viruses, most of which exert a destructive impact on thousands of colonies. The occurrence of resistance to the therapeutic substances used against these organisms is rising, and the residue from these chemicals may accumulate in honey bee products, subsequently affecting the human health. There is current advice to avoid the use of antibiotics, antifungals, antivirals, and other drugs in bees, and therefore, it is necessary to develop alternative strategies for the treatment of bee diseases. In this context, the impact of nosema diseases (nosemosis) on bee health and the negative insults of existing drugs are discussed. Moreover, attempts to combat nosema through the use of alternative compounds, including essential oils, plant extracts, and microbes in vitro and in vivo, are documented.Plan of High end Foreign Experts of the Ministry of Science and Technology | Ref. G2022016009

In vivo diabetic wound healing effect and HPLC–DAD–ESI–MS/MS profiling of the methanol extracts of eight Aloe species

Genus Aloe, Xanthorrhoeaceae, is well distributed all over Egypt, and many species have been used as medicinal plants; mainly reported to prevent cardiovascular diseases, cancer and diabetes. This study attempts to analyze the secondary metabolites in the methanol extract of the leaves of eight Aloe species; A. vera (L.) Burm. f., A. arborescens Mill., A. eru A. Berger, A. grandidentata Salm-Dyck, A. perfoliata L., A. brevifolia Mill., A. saponaria Haw. and A. ferox Mill. growing in Egypt. For this aim HPLC–DAD–MS/MS in negative ion mode was used. Although belonging to the same genus, the composition of each species presented different particularities. Seventy one compounds were identified in the investigated Aloe species, of which cis-p-coumaric acid derivaties, 3,4-O-(E) caffeoylferuloylquinic acid and caffeoyl quinic acid hexoside were the most common phenolic acids identified. Aloeresin E and isoaloeresin D, 2′-O-feruloylaloesin were the common anthraquinones identified. Lucenin II, vicenin II, and orientin were the common identified flavonoids in the investigated Aloe species. 6′-Malonylnataloin, aloe-emodin-8-O-glucoside, flavone-6,8-di-C-glucosides could be considered as chemotaxonomic markers for the investigated Aloe species. The eight Aloe species had significant anti-inflammatory activity, in addition to the significant acceleration of diabetic wound healing in rats following topical application of the methanol extracts of their leaves. This is the first simultaneous characterization and qualitative determination of multiple phenolic compounds in Aloe species from locally grown cultivars in Egypt using HPLC–DAD–MS/MS, which can be applied to standardize the quality of different Aloe species and the future design of nutraceuticals and cosmetic preparations. Keywords: Aloe, HPLC–DAD–MS/MS, Chemotaxonomic, Anti-inflammatory, Wound healin

Novel Thiazole Derivatives of Medicinal Potential: Synthesis and Modeling

This paper reports on the synthesis of new thiazole derivatives that could be profitably exploited in medical treatment of tumors. Molecular electronic structures have been modeled within density function theory (DFT) framework. Reactivity indices obtained from the frontier orbital energies as well as electrostatic potential energy maps are discussed and correlated with the molecular structure. X-ray crystallographic data of one of the new compounds is measured and used to support and verify the theoretical results

Immunization with outer membrane proteins (OprF and OprI) and flagellin B protects mice from pulmonary infection with mucoid and nonmucoid Pseudomonas aeruginosa

Background: Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium, which considered as a common cause of nosocomial infection and life-threatening complications in immunocompromized and cystic fibrosis patients. Here, we evaluate the protective effect of recombinant vaccines composed of outer membrane proteins OprF and OprI alone or in combination with flagellin B against mucoid and nonmucoid pseudomonas infection. Methods: BALB/C mice were immunized subcutaneous using OprF and OprI with or without flagellin B and antibody titers were determined. Serum bactericidal and opsonophagocytosis activities of immunized and control sera were estimated against mucoid and nonmucoid pseudomonas strains. Lung tissue sections from immunized and nonimmunized mice were analyzed and the levels of peripheral neutrophils infiltration into the lung and tissue inflammation were scored. Results: Subcutaneous immunization using OprF and OprI with or without flagellin B elicited higher antibody titers against OprF, OprI, and flagellin B. The produced antibodies successfully opsonized both mucoid and nonmucoid strains with subsequent activation of the terminal pathway of complement that enhances killing of nonmucoid strains via complement-mediated lysis. Furthermore, opsonized mucoid and nonmucoid strains showed enhanced opsonophagocytosis via human peripheral neutrophils, a mechanism that kills P. aeruginosa when complement mediated lysis is not effective especially with mucoid strains. Immunized mice also showed a significant prolonged survival time, lower bacteremia, and reduced lung damage when compared with control nonimmunized mice. Conclusion: Our data showed that mice immunized with OprF/OprI or OprF/OprI and flagellin B are significantly protected from infection caused by mucoid and nonmucoid strains of P. aeruginosa

Design, synthesis of new pyrimidine derivatives as anticancer and antimicrobial agents

<p>A new series of 6-aryl-5-cyano thiouracil derivatives were synthesized. Cyanouracil <b>1</b> was condensed with monochloroacetic acid and different aldehydes to give thiazolopyrimidine <b>2</b>. On the other hand, treatment of cyanouracil <b>1</b> with 2-chloro-<i>N</i>-substituted-phenylac etamide afforded <b>4</b>. Hydrazinolysis of <b>6</b> afforded the hydrazino derivatives <b>7</b> which upon reaction with different electrophilic reagents such as acetic anhydride, benzoyl chloride, and carbon disulfide yielded pyrimidine derivatives <b>8</b>–<b>15</b>. Some of the new derivatives were explored for their antimicrobial activities. Compounds <b>7</b> and <b>9</b> have a promising activity, relatively equipotent to the reference drug. All of the new synthesized compounds were tested <i>in vitro</i> for their antiproliferative activities against HePG-2 and MCF-7 cell lines. Compounds <b>7</b>, <b>9</b>, and <b>2d</b> displayed potent growth inhibitory effect toward the two cell lines more than the standard drug 5-FU. Furthermore, a docking study of the most active compounds was performed with thymidylate synthase enzyme.</p

6-Iodo-2-isopropyl-4<i>H</i>-3,1-benzoxazin-4-one as building block in heterocyclic synthesis

<p>As a part of ongoing studies in the synthesis of a variety of heterocycles of biological importance, we report here an efficient and convenient method for the synthesis of novel compounds from 6-iodo-2-isopropyl-4<i>H</i>-3,1-benzoxazin-4-one <b>1</b> as building block. The reaction of benzoxazinone <b>1</b> with various reagents such as diethylmalonate, sodium azide, and phosphorus pentasulfide yielded the compounds <b>2–5</b>. The behavior of benzothiazin-4-thione <b>5</b> toward formamide and hydrazine hydrate was investigated, forming the compounds <b>6</b> and <b>7</b>. The reaction of quinazolinone derivative <b>8</b> with β-D-glucose pentaacetate, ethyl 2-methyl-5-((1S,2R,3R)-1,2,3,4-tetrahydroxybutyl)furan-3-carboxylate, epichlorohydrin and benzenesulphonyl chloride afforded quinazolinone derivatives <b>9, 10, 12,</b> and <b>13</b> respectively. The reaction of quinazolinone derivative <b>10</b> with acetic anhydride resulted in formation of the acylated compound <b>11</b>. The behavior of quinazolinylacetohydrazide derivative <b>14</b> toward carbon electrophiles^[<a href="#CIT0016" target="_blank">¹⁶</a>^] has been investigated by its reaction with ethyl benzoylacetate, potassium thiocyanate, and phenyl isothiocyanate, affording the quinazolinone derivatives <b>15, 16,</b> and <b>18</b>, respectively. Treatment of compound <b>16</b> with sodium hydroxide followed by hydrochloric acid yielded the mercapto-triazole derivative <b>17</b>. The structures of the newly synthesized compounds were confirmed by elemental analysis, infrared (IR), ¹H NMR, ¹³C NMR, and mass spectra. The antimicrobial activities of some of the synthesized compounds were preliminarily evaluated.</p

Regioselectivity and regiospecificity of benzoxazinone (2-isopropyl-4<i>H</i>-3,1-benzoxazinone) derivatives toward nitrogen nucleophiles and evaluation of antimicrobial activity

<p>A novel group of 6-iodoquinazolin-4(<i>3H</i>)-one derivatives was prepared. The reaction of the benzoxazinone <b>3</b> with various nitrogen nucleophiles such as formamide and hydrazine hydrate and also the reaction of the isopropylquinazolinone <b>4</b> with hydrazonyl chloride have been shown to proceed with a high degree of regioselectivity at C(2). Spiro heterocycles have been found to play fundamental roles in biological processes and have exhibited diversified biological activity and pharmacological and therapeutical properties; thus reaction of acetohydrazides <b>10a–c</b> afforded the spiro compounds <b>11a–c</b>. The acetohydrazide derivative <b>7</b> reacted with carbon electrophiles such as acetylacetone, ethyl acetoacetate, acid chlorides, and benzaldehyde to give some interesting heterocyclic compounds <b>12–16</b>, respectively. The structures of all the synthesized compounds were inferred by infrared, ¹H NMR, and mass spectra as well as elemental analyses. The antimicrobial activities of some of the synthesized products were preliminarily evaluated.</p