Synthesis and in vivo anti-hyperlipidemic activity of novel n-benzoylphenyl-2-furamide derivatives in Wistar rats

Purpose: To synthesize and evaluate the anti-hyperlipidemic activity of a novel series of N- (benzoylphenyl)-2-furamides (3a, 3b, 4a, 4b and 4c).Methods: Compounds (3a, 3b, 4a, 4b and 4c) were successfully synthesized by reacting activated furan-2-carbonyl-chloride derivatives with aminobenzophenones at 60 °C for 36 h. Hyperlipidemia was induced in overnight fasted rats by intraperitoneal administration of Triton WR-1339 (300 mg/kg). to overnight fasted rats. The rats were divided into six groups: control, hyperlipidemic, hyperlipidemic plus compounds 3b, 4b, 4c, and hyperlipidemic plus bezafibrate-treated. Eighteen hours later, blood samples were collected and plasma lipid profile determined using enzymatic methods.Results: At a dose of 15 mg/kg body weight, the elevated plasma triglyceride (TG) levels, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels were significantly reduced by compounds 4b (p < 0.001) and 4c (p < 0.0001) 18 h later, compared to the hyperlipidemic group. Furthermore, compounds 4b and 4c significantly increased high density lipoprotein cholesterol (HDL-C) levels by 29 and 34 %, respectively.Conclusion: The findings indicate the high potency of N-(benzolphenyl)-2-furamides (4b and 4c) as lipid-lowering agents. Thus, these compounds 4b and 4c may used as lead compounds for the development of new derivatives and agents for targeting dyslipidemia and cardiovascular diseases.Keywords: Triton WR-1339-induced hyperlipidemic rats, N-(benzoylphenyl)-2-furamides, Lipid-lowering activity, Cardiovascular disease, Synthesi

New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation

Phosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new N\u27-(diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (1H and 13C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effect against the human colon carcinoma (HCT-116) cell line. Our cheminformatics analysis indicated that the para-tailored derivatives [p-NO2 (3) and p-CF3 (7)] have better ionization potentials based on calculated Moran autocorrelations and ionization potentials. Subsequent in vitro cell proliferation assays validated our cheminformatics results by providing experimental evidence that both derivatives 3 and 7 exhibited improved antiproliferative activities against HCT-116. Hence, our results emphasized the importance of electron-withdrawing groups and hydrogen bond-acceptors in the rational design of small-molecule chemical ligands targeting PI3Kα. These results agreed with the induced-fit docking against PI3Kα, highlighting the role of p-substituted aromatic rings in guiding the ligand-PI3Kα complex formation, by targeting a hydrophobic pocket in the ligand-binding site and forming π-stacking interactions with a nearby tryptophan residue

Design , Synthesis and Biological Evaluation Of Sulfonic Acid Esters / Benzene sulfonamides As Potential CETP Inhibitors

Cholesteryl ester transfer protein (CETP) is a glycoprotein involved in transporting lipoprotein particles and neutral lipids between high-density lipoprotein (HDL) and low density lipoproteins (LDL) and therefore it\u3es a proper target for treating dyslipidemia and related disorders, Guided by our previously-reported pharmacophore and QSAR models for CETP inhibition, we synthesized and bio assayed a series of toluene-4-sulfonic acid 4-benzylamino-phcnyl ester (8a-8m)/ N-(4-benzyl-phenyl)-4-methyl- benzene sulfonamide (6a-61) derivatives. The proposed structures for compounds 6a-1 and 8a-m were confirmed via elemental analyses, IR spectroscopy. mass spectroscopy, lH- and 13C-NMR spectra. The most potent synthesized compound 6j illustrated anti-CETP ICSO 0f 3.4 uM

Design, Synthesis, and Biological Evaluation of Benzylamino- Methanone Based Cholesteryl Ester Transfer Protein Inhibitors

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Synthesis and In Vivo Hypolipidemic Effect of Some N-(Benzoylphenyl)-Carboxamide Derivatives in Triton WR-1339-Induced Hyperlipidemic Rats

A series of N-(benzoylphenyl)-carboxamide derivatives (2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, 6a and 6b) was prepared with good yields by reacting the corresponding carbonyl chlorides with aminobenzophenones at room temperature. This was followed by evaluating the hypotriglyceridemic and hypocholesterolemic effects of 3b, 5a and 5b. Triton WR-1339 (300 mg/kg) was intraperitoneally administered to overnight-fasted rats to induce hyperlipidemia. Rats were divided into six groups: control, hyperlipidemic, hyperlipidemic plus compounds 3b, 5a and 5b and hyperlipidemic plus bezafibrate. Results showed that after 18 h of treatment at a dose of 15 mg/kg body weight of each of the test compounds, the elevated plasma levels of triglycerides (TG) and total cholesterol (TC) were significantly lowered by compounds 5b and 3b (p < 0.001) and by 5a (p < 0.0001), compared to the hyperlipidemic control group. Compounds 3b and 5a significantly increased levels of high-density lipoprotein cholesterol (HDL-C) by 58 and 71%, respectively. In addition, compounds 3b and 5a caused significant reduction (p < 0.0001) of low-density lipoprotein cholesterol (LDL-C) levels compared to the control group. These results suggest a promising potential for compounds 3b, 5a and 5b as lipid-lowering agents, which may contribute to reducing the risk of atherosclerosis and cardiovascular disease

Preparation of Mucoadhesive Oral Patches Containing Tetracycline Hydrochloride and Carvacrol for Treatment of Local Mouth Bacterial Infections and Candidiasis

The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydrochloride and carvacrol in an attempt to develop a novel oral drug delivery system for the treatment of mouth infections. The bilayered patches were prepared using ethyl cellulose as a backing layer and carbopol 934 as a matrix mucoadhesive layer. Patches were prepared with different loading amounts of tetracycline hydrochloride and carvacrol. The antimicrobial activity was assessed for the prepared patches using the disc-diffusion method against the yeast Candida albicans and five bacterial strains, including Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Bacillus bronchispti. In this work, we highlighted the possibility of occurrence of a synergistic action between carvacrol and tetracycline. The best formulation was selected based on microbiological tests, drug release, ex-vivo mucoadhesive performance, and swelling index. Physical characteristics of the selected formulations were determined. These included pH, patch thickness, weight uniformity, content uniformity, folding endurance, and patch stability

Synthesis and Anti-Hyperlipidemic Evaluation of N‑(Benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide Derivatives in Triton WR-1339-Induced Hyperlipidemic Rats

The lipid-lowering activity of a series of novel N-(benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide derivatives has been studied in Triton WR-1339-induced hyperlipidemia in rats. The test animals were divided into four groups: control, hyperlipidemic, compound + 4% DMSO [C1: N-(2-benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide (1), C2: N-(3-benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide (2), C3: N-(4-benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide (3)]-treated and bezafibrate (BF)-treated. At a dose of 15 mg/Kg body weight, compounds 2, 3 and BF significantly reduced elevated plasma triglycerodes levels after 12 h. Moreover, high density lipoprotein-cholesterol levels were significantly increased in all treated groups after 12 h compared to the hyperlipidemic control group, except for C1 which was inactive. In sum, it may be stated that the results of the present study demonstrated new properties of some N-(benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide derivatives as potent lipid lowering agents and these beneficial activities may contribute to their cardioprotective and antiatherosclerotic role