Kamelia M. Amin

Synthesis and preliminary evaluation of some substituted coumarins as anticonvulsant agents.

Some new substituted coumarinylthiazolines, coumarinylthiazolidin-4-ones, and substituted chromenothiazoles were synthesized and evaluated for anticonvulsant activity. Some selected compounds were assayed against seizures induced by pentylenetetrazole (PTZ) and strychnine in mice. Compounds 3b, 6b, and 7b were the most active of the series against PTZ induced seizures. Compound 7b provided anticonvulsant activity (PD(50)=95mg/kg, ip) at a dose 200mg/kg compared to phenobarbital (PD(50)=16mg/kg, ip) at a dose 30mg/kg (90% protection). No clear correlation was observed between the antiepileptic activity and molecular lipophilicity descriptors of the tested compounds.

Synthesis, anticoagulant and PIVKA-II induced by new 4-hydroxycoumarin derivatives

The action of the coumarin-type drugs and related compounds is reviewed to their VKOR antagonistic effects. In our study, twenty 3-pyridinyl, pyrimidinyl and pyrazolyl-4-hydroxycoumarin derivatives were synthesized. A comparative in vivo (CT, PT determination) and in vitro (measurement of PIVKA-II levels) anticoagulant study with respect to warfarin showed that the synthesized compounds have different anticoagulant activities, the most prospective compounds were the 3-pyrazolyl-4-hydroxycoumarin derivatives.

Synthesis of New 7-Oxycoumarin Derivatives As Potent and Selective Monoamine Oxidase A Inhibitors

New series of 4-methyl and 3,4-dimethyl-7-oxycoumarin derivatives (oxadiazoles, thiadiazoles, triazoles, and thiazolidinones) were designed, synthesized, and evaluated for their monoamine oxidase (MAO) A and B inhibiting effect. All the synthesized compounds showed in vitro high affinity and selectivity toward MAO-A isoenzyme, compared to clorgyline and moclobemide, with Ki values on the picomolar range. Moreover, most of the tested compounds displayed MAO inhibitory effect when tested in vivo. The docking experiments carried out on MAO-A and MAO-B structures proved new information about the enzyme-inhibitor interaction and the potential therapeutic application of 7-oxycoumarin scaffold.

New quinoxaline 1, 4-di-N-oxides: Anticancer and hypoxia-selective therapeutic agents

A new series of quinoxaline 1,4-di-N-oxides was synthesized and evaluated for antitumor and hypoxic-selective cytotoxic activities. Antitumor activity against liver carcinoma (Hepg2) and brain tumor (U251) human cell lines were evaluated, among the tested compounds, 5b and 9b exhibited potential cytotoxic effect against Hepg2 with IC50 values of 0.77 and 0.50 microg/mL respectively, whereas, all the tested compounds lack antitumor activity against U251 human cell line. Moreover, compound 4 was the most potent hypoxia selective-cytotoxin on EAC cell line; IC50 2.5 microg/mL, potency 22 microg/mL, and was approximately 5.4-times more selective cytotoxin (HCR>40) than 3-amino-2-quinoxalinecarbonitrile1,4-dioxide (standard, HCR>7.4). Compounds 8b and 9b were more selective than the standard.

First Synthesis of Thiophene Thioglycosides

A new method for the preparation of a new class of thiophene thioglycosides via one-pot reaction of the sodium thiophenethiolate salts with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galacto-pyranosyl bromides has been studied. The sodium thiophenethiolate salts are prepared using cyano-di-thioic analogs and their corresponding mono- and dithiolate salts.

New Trends in Synthesis of Pyrazole Nucleosides as New Antimetabolites

Pyrazole nucleosides and condensed pyrazole nucleosides exhibit various biological activities. This article describes recent synthetic approaches to their preparation, chemical properties, biological activities, and structure-activity relationships, with emphasis to selected drugs or drug candidates. Two pyrazole C-nucleoside compounds pyrazofurin (pyrazomycin) and its α-epimer pyrazofurin B are active components of potent antivirals approved for therapeutic use in human medicine aimed against various diseases caused by DNA viruses.

First Synthesis of Thienopyrazole Thioglycosides

Reported is the first method to prepare a new class of thienopyrazole thioglycosides via a one‐pot reaction of the sodium thienopyrazolthiolate salts with 2,3,4,6‐tetra‐O‐acetyl‐α‐D‐gluco‐and galactopyranosyl bromides. The sodium thienopyrazolthiolate salts are prepared using pyrazoldithioic acids and their corresponding mono ‐ and dithiolate salts.

New series of 6-substituted coumarin derivatives as effective factor Xa inhibitors: Synthesis, in vivo antithrombotic evaluation and molecular docking

Despite recent progress in antithrombotic therapy, theres still an unmet medical need for safe and orally available anticoagulants. Encouraged by the marked antithrombotic and anticoagulant activities of some coumarin derivatives, twenty-three new N-coumarinyl-4-amidinobenzamides 4a-f and 6-heterocycle substituted coumarin derivatives 5, 6a,b, 10a-e, 12a-e and 14a-d were synthesized and evaluated for their in vivo antithrombotic activity. The most active congeners were the unsubstituted amidine 4a (36.5 s), coumarinyl oxadiazole 5 (42.3 s), bis coumarinyl oxadiazole 6b (37.8 s) and coumarinyl pyrazole 10b (38.5 s) that presented prothrombin time (PT) values comparable to the reference drug warfarin (42.3 s). Furthermore, docking studies were undertaken to gain insight into the possible binding mode of these compounds with the coagulation factor Xa (FXa) binding site.

Monoamine oxidase A and B inhibiting effect and molecular modeling of some synthesized coumarin derivatives.

New series of bioactive 7-oxycoumarin derivatives were synthesized and tested for their in vitro and in vivo monoamine oxidase (MAO) A and B inhibitory effect. In vitro studies revealed exceptionally potent and selective MAO-A inhibitors with K(i) values on a picomolar range. The acetohydrazide (3b) and the dioxopyrrolidine derivative (7b) showed the most potent in vitro and in vivo MAO inhibition activity. Moreover, molecular modeling study of the synthesized compounds into MAO-A (PDB: 2Z5X) and MAO-B (PDB: 2XFN) binding sites exhibited direct correlation between AutoDock binding affinity and% inhibition MAO-A (pM) and MAO-B (μM). In addition, the results of in vivo MAO inhibiting properties (ED(50)) of the tested compounds revealed better direct correlation.

Design, Synthesis and In vitro Anti-tumor Evaluation of Novel Acrylohydrazide Thioglycosides

A facile, convenient and high yielding synthesis of novel Acrylohydrazide thioglycosides via one-pot reaction of the potassium thiolate salts of aglycon part - prepared from readily available starting materials - with 2,3,4,6-tetra-O-acetyl- α-D-gluco- and galactopyranosyl bromides . Pharmacological evaluation of compounds 8j, 8b, 8h, 8k, 8f and 5b in vitro against (MCF-7) cell line (Breast carcinoma cell line) showing high- moderate anti-tumor activities with IC50 values ranging from 3.69-14.93 (μM), moreover molecular modeling of these compounds revealed that they have high binding affinity through hydrophobic-hydrophobic interaction and moderate selectivity through the hydrogen bond interaction with the atypical nucleotide binding pocket in the amino terminus of Hsp90.