Letters in Drug Design & Discovery - Volume 13, Issue 8, 2016

Background: For studying the antioxidant activity a synthesized 1,3-bis(3-phenylpropyl-1)- 1,3-dihydro-2H-benzimidazol-2-imine hydrobromide (M1) has been chosen because of its most pronounced antiproliferative effect (preliminary studies) to human colorectal cancer cell line HT-29, breast cancer cells MDA-MB-231 and its nontoxicity to normal Lep 3, determined by means of MTS-test. It is believed that this suppressive activ Read More

A novel tamibarotene derivative was synthesized by coupling cytotoxic agent 5-Fluorouracil (5-FU) with tamibarotene via ester. This hybrid drug (compound 10) was evaluated for its antiproliferative activities against human leukemic U937, HL-60 and K562 cell lines in vitro. Results showed that compound 10 exhibited more potent anti-leukemic activity than the positive control tamibarotene. Furthermore, the preliminary sta Read More

N,N’-bis[1-(substitutedphenyl)-3-(morpholine-4-yl)propylidene]hydrazine dihydrochlorides, N1-N11 were designed and synthesized as cytotoxic agents. These compounds were synthesized by the reaction of 2 moles of 1- (substitutedphenyl)-3-(morpholine-4-yl)-1-propanone hydrochlorides with 1 mole of hydrazine hydrate. The compounds reported here are new, except N1 and N4. The cytotoxicity of the compounds was tes Read More

Melanin is a pigment distributed in the human body. The excess accumulation of melanin contents on skin surface induces mottling and freckles which are unfavorable for maintaining good health and beauty. On the other hand, gray hair is caused by the decreasing of melanin production. Hence, to maintain appropriate melanin level in human body is desired strongly. Melanin is biosynthesized in melanosome in melanocyte Read More

Time-dependent distribution of selegiline was monitored in various tissues of rabbits treated with a dose of 30 mg/kg intravenously. Selegiline content was determined by validated RPHPLC method following 5,15, 30, 60 and 120 minutes of treatment. The present study confirming earlier data showed that selegiline readily penetrates through the blood brain barrier, however, as a new result, high selegiline concentrations Read More

Quantitative structure-activity relationship (QSAR) and molecular modeling studies have been performed on a series of indole-based pyridone analogues as hepatitis C virus (HCV) NS5B polymerase inhibitors. A multiple linear regression (MLR) analysis has shown that the presence of hydrogen- bond donors in the molecule plays a negative role, but the substituents present on the indole ring sterically favor the activity Read More

Acyclovir, a popular antiviral drug, is associated with the problems of poor water solubility, low bioavailability (15-30%), low permeability (across the gastro intestinal membrane) and short half-life (3 hours) leading to high dosage frequency which in turn may cause adverse effects. Therefore, with the objective of the improvement in solubility (and dissolution also) and gastro intestinal permeability (which in turn is expected to impro Read More

The Objective of the present work was to enhance the solubility and dissolution profile of poorly water soluble BCS class II drug Tinidazole (TNZ). Microwave energy was utilized to prepare solvent free solid dispersions of TNZ and combination of TNZ with hydrophilic carriers as urea, gum acacia, β cyclodextrin (β CD), polyethylene glycol 6000 and polyvinyl pyrolidone Formulated solid dispersions were characterized by FTIR Read More

The close structural similarity between cyclooxygenase (COX) isoforms and also the lack of potent selective COX-2 inhibitors with low side effects, stimulate the development of new highly selective COX-2 inhibitors. In this study, a group of imidazo[1,2-a]pyridines was designed, synthesized and investigated to identify potent and selective COX-2 inhibitors. In vitro COX inhibition assay showed that all derivatives were selective COX Read More

A series of 2-((5-aryloxy-1-methyl-3-methyl-1H-pyrazol-4-yl)methylene) hydrazinecarboxamides (6a-6l) and 2-((5-aryloxy-1-methyl-3-phenyl-1H-pyrazol-4-yl)methylene) hydrazinecarboxamides (7a-7l) were designed and synthesized. The maximal electroshock shock (MES) and subcutaneous pentylenetetrazole (sc-PTZ) seizure models in mice were used to evaluate the antiepileptic effect of compounds synthesized. Further, th Read More

With the help of computer-aided drug design approach, five dabigatran derivatives were designed and synthesized. The structures of these compounds were elucidated by 1H NMR, 13C NMR, HRMS analyses. All the compounds were evaluated for their thrombin inhibitory activitiy in vitro (IC50) and they showed significant thrombin inhibition with IC50 values from 2.74 to 20.31 nM. Especially, compound 7a, and 7b were po Read More

A series of thirteen (2E)-1-[4-({6-nitro-2-[(E)-2-phenylvinyl]quinolin-4-yl}amino)phenyl]- 3-[(substituted) phenyl]prop-2-en-1-ones (5a-5m) were synthesized by five-step synthesis starting from 4-nitroaniline via 2-methyl-6-nitroquinolin-4-ol (2), 4-chloro-2-methyl-6-nitroquinoline (3), 4- chloro-6-nitro-2-[(E)-2-phenylethenyl]quinoline (3), and 1-[4-({6-nitro-2-[(E)-2-phenylvinyl]quinolin- 4-yl}amino)phenyl]ethanone (5), respectivel Read More

ATP-dependent xenobiotic efflux transporter P-glycoprotein (P-gp) limits the cellular accumulation of many therapeutically important drug molecules. The most prominent of these are CNS active compounds and the potential chemotherapeutic agents. Co-administration of chemotherapeutic agents with modulators of P-glycoprotein has been advocated as a promising concept to circumvent drug resistance i Read More

A series of novel 3-[2-(4H-1,2,4-triazol-4-yl)ethyl]-1-alkyl-1H-indole derivatives (4a-s) were synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using maximal electroshock (MES) and rotarod neurotoxicity (TOX) tests. Among the compounds studied, compound 3-[2-(4H-1,2,4-triazol-4-yl)ethyl]-1-nonyl-1H-indole (4p) was found by intraperitoneal (i.p.) administration in mice to be the most potent co Read More

Chromone derivatives, which have activities on the central nervous system (CNS) may be of great importance for finding out drugs for treatment of CNS disorders. Discovery of natural products with affinity for serotonin or 5- hydroxytryptamine (5-HT) receptors is the limelight of current research. Hence, the current objective of the present work is to study the 5-HT2B antagonist activity of 2-(2-phenylethyl)chromone (PEC Read More