Ibrahim F. Nassar

A convenient synthesis and molecular modeling study of novel pyrazolo[3,4-d]pyrimidine and pyrazole derivatives as anti-tumor agents

Abstract An efficient method to obtain ethyl 5-amino-1-tosyl-1H-pyrazole-4-carboxylate (3) was outlined using condensation reactions of 4-methylbenzenesulfonylhydrazide with (E)-ethyl 2-cyano-3-ethoxyacrylate. The cyclocondensation reaction of this substrate and its hydrazide derivative with urea, thiourea, formamide, formic acid, d-glucose, o-phenylenediamine, 4-dimethylaminobenzaldehyde, anthracene-9-carbaldehyde, thioglycolic acid and carbon disulphide then with hydrazine hydrate analogues furnished a series of pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-d]oxazin-4-one, pyrazole-4-glucoside, 4-benzo[d]imidazole, 1,3-thiazolidinone, 1,3,4-oxadiazol-2(3H)-thione and 1,2,4-triazol-5(4H)-thione derivatives respectively. The structure of the compound 3 was supported by X-Ray crystallographic data. Orally administrated, one of each of the series of pyrazoles showed significant effects in mouse tumor model cancer cell lines (EAC) and two human cancer cell lines of Colon cancer (HCT-29) and Breast cancer (MCF-7) with docking studies.

Synthesis of Heterobicyclic Nitrogen Compounds as Molluscicide Agents Derived from 6-Methyl-5-styryl-1,2,4-triazin-3-thiol: Part I

Some new heterocyclic nitrogen compounds 1-14 have been synthesized from cyclization of 5-styryl-3-mercapto-6-methyl-1,2,4-triazines 1 with active methylene and/or nitrogen compounds and were evaluated as molluscicidal agents. Significant molluscicidal activities for some of the products towards Biomophalaria Alexandrina snails were observed.

Ethyl 5-amino-1-[(4-methyl­phen­yl)sulfon­yl]-1H-pyrazole-4-carboxyl­ate

In the title molecule, C13H15N3O4S, the benzene and pyrazole rings are inclined to each other at 77.48 (3)°. Two amino H atoms are involved in bifurcated hydrogen bonds, viz. intramolecular N—H⋯O and intermolecular N—H⋯O(N). The intermolecular hydrogen bonds link the molecules related by translation in [100] into chains. A short distance of 3.680 (3) Å between the centroids of benzene and pyrazole rings from neighbouring molecules shows the presence of π–π interactions, which link the hydrogen-bonded chains into layers parallel to the ab plane.

Design, synthesis and anticancer evaluation of novel pyrazole, pyrazolo[3,4-d]pyrimidine and their glycoside derivatives

ABSTRACT The chalcone derivatives 3a,b were cyclized upon reaction with thiourea to give the pyrazolo[3,4-d]pyrimidine derivatives 5a,b. Condensation of 5a,b and their hydrazide derivatives 8a,b with cyclic and acyclic glucose gave the condensed S- and N-glycosides 7a,b and 9a,b, respectively. Reaction of 3b with ethyl cyanoacetate followed by reaction with cyclic glucose afforded a mixture of the O- and/or N-glycoside isomers 12 and 13, respectively. The pyrazolo[3,4-c]pyrazole derivative 14 was also obtained from the reaction of 3b with hydrazine hydrate. A number of the synthesized compounds were screened for their antitumor activity against three different tumor cell lines HEPG2 (liver), HCT116 (colon) and MCF-7 (breast) with a docking study against CDK2.

Utility of thiophene-2-carbonyl isothiocyanate as a precursor for the synthesis of 1,2,4-triazole, 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives with evaluation of their antitumor and antimicrobial activities

Abstract The reaction of thiophene-2-carbonyl isothiocyanate with phenylhydrazine gave 1-phenyl-5-(thien-2-yl)-1,2,4-triazole-3-thiol which was transformed by follow-up reactions into derivatives substituted in the 3-position by 1,2,4-oxadiazole and 1,2,4-thiadiazole moieties via thioethers linkages. The antitumor activity of the products against two human tumor cell lines, namely hepatocellular carcinoma HePG-2 and mammary gland breast cancer MCF-7 as well as the antimicrobial activity of some of these compounds was evaluated. Graphical Abstract

Design, Synthesis of Novel Pyridine and Pyrimidine Sugar Compounds as Antagonists Targeting the ERα via Structure-Based Virtual Screening

BACKGROUND New aryl substituted cyclohepta[b]pyridine and cyclohepta[d]pyrimidine derivatives were synthesized. The sugar hydrazones of the synthesized pyridine and pyrimidine compounds were also prepared. METHOD In addition, the 1,3,4-oxadiazolyl acyclic C-nucleoside analogs of the pyridine system were prepared. The hemolytic, prebiotic, anticancer and antimicrobial activities of some of the synthesized compounds were also studied. Compounds 10 and 12 showed high activity against MCF-7, HEPG-2 and HCT-116 cell lines with IC50 at range 3.56-8.55 µg/mL. In addition, the synthesized condensed thiopyrimidine derivative 10 exhibited more potent bactericidal activity while compound 7 demonstrated potent antifungal activity against Aspergillus niger. Furthermore, the synthetic compounds of the pyrimidine base promoted the growth of lactic acid bacteria. RESULTS The predicted binding patterns of three of the prepared derivatives as possible antagonists against ERα were investigated which showed good binding patterns.