Medicinal Chemistry - Volume 9, Issue 7, 2013

Tuberculosis, caused by Mycobacterium tuberculosis, is amongst the foremost infectious diseases. Treatment of tuberculosis is a complex process due to various factors including a patient’s inability to persevere with a combined treatment regimen, the difficulty in eradicating the infection in immune-suppressed patients, and multidrug resistance (MDR). Extensive research circumscribing molecules to counteract this disease h Read More

A new dihydropyranexanthone derived from the natural xanthone lichexanthone (1) was synthesised and, together with other 18 derivatives including ω-bromo and ω-aminoalkoxylxanthones (containing methyl, ethyl, propyl, tertbutylamino and piperidinyl moieties), were tested against Mycobacterium tuberculosis. Nine ω-aminoalkoxylxanthones showed good antimycobacterial activity, and their in vitro cytotoxicity was d Read More

A 30-membered piperidine ring-fused aromatic sulfonamide library was synthetized, including N-arylsulfonyl 1,2,3,4-tetrahydroquinolines, 1,2,3,4-tetrahydroisoquinolines and 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles. The compounds induced oxidative stress and glutathione depletion in HT168 melanoma and K562 leukemia cells and in micromolar concentrations exerted cytotoxic effects. Among the tested sulfonamides, Read More

Based on the structure of 23-hydroxybetulinic acid (1), a series of 28-amide derivatives were synthesized. Biological evaluation in vitro for their antitumor activities against five cell lines (A549, BEL-7402, SF-763, B16 and HL-60) has indicated that compound 6g possesses the most effective antitumor activity with an IC50 value of 10.47 µM when treated with HL-60 cells. In vivo testing has also shown a comparable activity of Read More

Acetogenins are among the most potent of the known inhibitors of complex I (NADH-ubiquinone oxidoreductase) in mitochondrial electron transfer system. Elucidation of the dynamic function of the alkyl spacer linking the two toxophores (i.e., the hydroxylated tetrahydrofuran and the γ-lactone rings) is critical for fully understanding their inhibition mechanism. To this end, using molecular dynamics simulations a structure-activity Read More

A series of novel imidazolone derivatives were designed and synthesized via a rational drug design strategy. These compounds were obtained from 3-substituted imidazolidine-2,4-dione through alkylation, formylation, dehydration, and amination. The structures were characterized by 1H NMR, 13C NMR, and MS. All target compounds were screened for their DPP-4 inhibitory activity in vitro. The results revealed that some imidaz Read More

A series of ferulic acid amides with extended P1' groups were synthesized and tested for their inhibitory activities on matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9. Preliminary structure–activity relationship analysis and docking studies indicated that ferulic acid amides with electron-donating groups at the amino phenyl ring showed better inhibitory activities and selectivity than those with electron-withdrawin Read More

The emergence of mutant virus in drug therapy for HIV-1 infection has steadily risen in the last decade. Inhibition of reverse transcriptase enzyme has emerged as a novel target for the treatment of HIV infection. The aim to decipher the structural features that interact with receptor, we report a quantitative structure activity relationship (QSAR) study on a dataset of thirty seven compounds belonging to bisphenylbenzimidazoles Read More

A series of novel 1,2,4-triazole thioacetanilide derivatives has been designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells. Half of these compounds showed moderate to potent activities against wild-type HIV-1 with an EC50 ranging from 38.0 µ;M to 4.08 µM. Among them, 2-(4-(2-fluorobenzyl)-5-isopropyl-4H-1,2,4-triazol- 3-ylthio)-N-(2-nitrophenyl)acetamide 7d was identified as the most promising co Read More

Breast cancer is one of the most high-profile malignant diseases in modern society. Among postmenopausal women affected by the disease, a substantial portion has breast tumors that are estrogen-receptor positive. A common therapeutic intervention for this type of cancer is through endocrine therapy. Endocrine agents can act by either diminishing the availability or inhibiting the binding of estrogens to ER. Aromatase Read More

Xylose is one of the most abundant carbohydrates in nature, and widely used to produce bioethanol via fermentation in industry. Xylulose can produce two key enzymes: xylose reductase and xylitol dehydrogenase. Owing to the disparate cofactor specificities of xylose reductase and xylitol dehydrogenase, intracellular redox imbalance is detected during the xylose fermentation, resulting in low ethanol yields. To overcome th Read More

L-type calcium channel (LTCC) blockers are used as cardiac antiarrhythmics or antihypertensives. In our previous research, we have reported a furanocoumarin, imperatorin, which exhibited potent vasodilatory effects. The possible mechanism might involve with inhibition against LTCC. In order to further investigate the pharmacologic mechanism of imperatorin for interaction with LTCC, the homology modeling of LTCC was Read More

Curcumin bioconjugates, with folic acid, fatty acids and dipeptide, have shown much lower MIC than curcumin against clinically isolated Gram-positive, S.viridians, and Gram-negative bacterial strains, E. coli, P. mirabilis and K. pneumoniae. Polynomial regression analysis was performed to establish a correlation between lipophilicity (logP) and antibacterial activity (pMIC), which showed the efficacy of these molecules against Read More

Ibuprofen is one of the most popular NSAIDs for the last three decades but also known for its gastrointestinal side effects similar to other NSAIDs. To overcome this problem, we have designed and synthesized ibuprofen - antioxidant (thymol, guaiacol, eugenol, and menthol) hybrids (6-13) with and without spacer as gastro sparing agents. The hybrids have been found to be chemically stable, biolabile and exhibited retention of a Read More