Korany A. Ali

Design, synthesis and structure-activity relationship study of novel pyrazole-based heterocycles as potential antitumor agents.

The versatile hitherto unreported 3-[(E)-3-(dimethylamino)acryloyl]-1,5-diphenyl-1H-pyrazole-4-carbonitrile (3) was prepared via the reaction of 3-acetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile (1) with dimethylformamid-dimethylacetal (DMF-DMA). The latter product and 3-((E)-3-morpholin-4-yl-acryloyl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (4) underwent regioselective 1,3-dipolar cycloaddition with nitrilimines to afford the corresponding pyrazole derivatives. In vivo anti-estrogenic activity and acute toxicity after single oral dose of the newly synthesized compounds were evaluated. In vitro disease-oriented primary antitumor screening utilizing 14 cell lines of breast and ovarian tumor subpanels has been also carried out. All tested compounds showed anti-estrogenic properties equipotent or superior to the reference drug, letrozole. 3-[3-(4-Cyano-1,5-diphenyl-1H-pyrazole-3-yl)-1-(4-methylphenyl)-1H-pyrazole-4-carbonyl]-1,5-diphenyl-1H-pyrazole-4-carbonitrile (27c) and 3-(3-acetyl-1-phenyl-1H-pyrazole-4-carbonyl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (8a) showed a significant cytotoxic activity in a nanomolar range against certain types of breast and ovarian tumors with tolerable toxicity.

Synthesis and Structure-activity Relationship Studies of Pyrazole-based Heterocycles as Antitumor Agents

Several 4‐cyano‐1,5‐diphenylpyrazoles attached to different heterocyclic ring systems at position 3 were synthesized starting from ethyl 4‐cyano‐1,5‐diphenyl‐1H‐pyrazole‐3‐carboxylate 1. The newly synthesized compounds were tested in vivo for their anti‐estrogenic effects and evaluated in vitro for their cytotoxic properties against estrogen‐dependent tumors. 3‐(5‐Mercapto‐1,3,4‐oxadiazole‐2‐yl)‐1,5‐diphenyl‐1H‐pyrazole‐4‐carbonitrile 13 revealed the highest cytotoxic activity with a GI50 value equal to 40 nM against the IGROVI ovarian tumor cell line. It also showed an anti‐estrogen activity 1.6 more effective than the reference drug, in addition to a high tolerable dose. 3‐(5‐(Methylthio)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1,5‐diphenyl‐1H‐pyrazole‐4‐carbonitrile 7 was found to have the highest anti‐estrogenic activity, while 1,5‐diphenyl‐3‐[5‐(phenylamino)‐1,3,4‐thiadiazol‐2‐yl]‐1H‐pyrazole‐4‐carbonitrile 11 showed the lowest activity. The oral LD50 values revealed that most of the tested compounds are relatively nontoxic.

Cytotoxic, antioxidant activities and structure activity relationship of some newly synthesized terpenoidal oxaliplatin analogs

The terpenoidal oxaliplatin derivatives (6) and (12) were newly synthesized using 2beta,3alpha-dihydroxy-11-oxo-18beta-olean-12-ene-30-oic acid (1) and 2alpha,2beta-dihydroxy-18beta-ursan-12-ene-28-oic acid (7) as starting materials. The synthesized compounds were evaluated for their cytotoxicity and antioxidant activities and were compared to Oxaliplatin and vitamin C as positive controls. Some of the compounds exhibited better cytotoxicity and antioxidant activities than the reference controls. The detailed synthesis, spectroscopic data, toxicity (LD(50)) and pharmacological screening for the synthesized compounds were reported.

Synthesis and Antimicrobial Evaluation of Some New Cyclooctanones and Cyclooctane-Based Heterocycles

The versatile synthon (E)‐2‐((dimethyl amino)methylene)cyclooctanone (2) was used as a key intermediate for the synthesis of cyclooctanones and cyclooctane‐based heterocycles with pyrazole, isoxazole, pyrimidine, pyrazolopyrimidine, triazolopyrimidine and imidazopyrimidine derivatives via its reactions with several nitrogen nucleophiles. The newly synthesized compounds were screened in vitro for their antimicrobial activity against pathogenic microorganisms (Listeria monocytogenes, methicillin‐resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans). Most of the tested compounds showed moderate to high antibacterial and antifungal effects against the tested pathogenic microorganisms. Among the synthesized compounds, 2‐((p‐sulfonamidophenyl)methylene)cyclooctanone (5) showed excellent activity against Listeria monocytogenes.

Studies With Pyrazol-3-Carboxylic Acid Hydrazide: The Synthesis of New Pyrazolyloxadiazole and Pyrazolyltriazole Derivatives

A simple and versatile method for the synthesis of pyrazol-3-yl-1,3,4-oxadiazole, pyrazol-3-yl-1,2,4-triazole, (1,5-diphenylpyrazol-3-yl)-(3,5-dimethyl-1-carbonyl)pyrazole, and (1,5-diphenylpyrazol-3-yl)-(5-hydroxy-3-metheyl-1-carbonyl)pyrazole derivatives from 1,5-diphenylpyrazole-3-carboxylic acid hydrazide has been developed.

Synthesis and Anticancer Properties of Silver(I) Complexes Containing 2,6-Bis(substituted)pyridine Derivatives

Several new 2,6-bis(substituted)pyridine ligands and 2,6-bis(substituted)pyridine Ag(I) nitrate complexes were synthesized and characterized spectroscopically. The newly synthesized ligands include pyridine-2,6-bis(3-oxopropanenitrile) (1), pyridine-2,6-bis(2-cyano-N-phenyl-3-oxopropanethioamide) (2), and pyridine-2,6-bis((E)-2-(2-phenylhydrazono)-3-oxopropanenitrile) (3). The newly synthesized ligands and silver(I) complexes were evaluated for their in vitro anticancer activity against four human cancer cell lines including hepatocellular carcinoma (HePG2), lung adenocarcinoma (A549), colon carcinoma (HT29), and breast adenocarcinoma (MCF7). Most of the newly synthesized silver(I) complexes exhibited better activity than the ligands, and the results have been compared with doxorubicin as a reference drug.

Synthesis and Reactions of 2-(Phenylthiocarbamoyl)-N-(Benzothiazol-2-Yl)-3-Phenyl-3-Oxopropanamide With Activated Chlorocompounds

GRAPHICAL ABSTRACT Abstract The versatile multifunctional unreported 2-(phenylthiocarbamoyl)-N-(benzothiazol-2-yl)-3-phenyl-3-oxopropanamide was prepared from N-(benzothiazol-2-yl)-3-phenyl-3-oxopropanamide. Several new series of poly-substituted thiophenes and 1,3,4-thiadiazoles incorporating the N-(benzothiazol-2-yl)-3-oxo-3-phenylpropanamide moiety were efficiently synthesized.

Synthesis, Anticancer Screening and Molecular Docking Studies of New Heterocycles with Trimethoxyphenyl Scaffold as Combretastatin Analogues.

BACKGROUND In this study, synthesis, molecular docking and anticancer screening of new series of substituted heterocycles with trimethoxy phenyl scaffold as Combretastatin analogues were described. Substituted pyridines were synthesized via the reaction of (E)-3-(dimethylamino)-1-(3,4,5- trimethoxyphenyl)prop-2-en-1-one (2) with active methylene reagents. Substituted pyrimidines were prepared by the reaction of the enaminone (2) with heterocyclic amines and 6-amino thiouracil. Furthermore, a series of pyrazoles substituted with trimethoxyphenyl scaffold were prepared by the reaction of the enaminone 2, with selected examples of hydrazonoyl halides. CONCLUSION The cytotoxic effect of the newly compounds was evaluated against HePG-2, HCT-116, MCF-7 and PC3 cancer cell lines. Among the new products, compounds 2, 3, 7 and 10 were found to exhibit promising results as anticancer agents. The IC50 values of 2, 3 and 7 were 54.6, 77.4 and 47.4 on PC3 respectively. Also, compound 2 had IC50 28.06 on MCF7. Moreover, the selectivity index indicated that compounds 2 and 3 are safe.

Design, Synthesis and In-vivo Anti-inflammatory Activity of New Celecoxib Analogues as NSAID

BACKGROUND A new series of Celecoxib analogues were easily synthesized via reactions of 4-(2-(1-chloro-2-oxopropylidene)hydrazinyl)benzene sulfonamide (1) with active methylene compounds and dialkyl malonate. In addition, compound 1 was reacted also with thiourea derivatives and thiosemicarbazone derivatives to afford thiazole derivatives 9 and 11, respectively. Furthermore, triazolo pyrimidine derivatives 13 were prepared via reaction of compound 1 with pyrimidine thione derivatives. The structures of the new synthesized compounds were assigned by elemental analysis and spectroscopic data. The new analogues were screened for their in vivo anti-inflammatory activity using carrageenan-induced paw edema method. CONCLUSION They showed moderate to good in vivo anti-inflammatory effects. Compounds 1, 6 and 11b were the most active compounds that reduced the paw edema induced by carrageenan by 12.25 %, 12.96 % and 12.97% respectively, as compared to the Indomethacin that inhibited the oedema volume by 7.47 %.

Crystal structure of 1,4-dihydro-1-phenylchromeno[4,3-c]pyrazole, C16H12N2O

Abstract C16H12N2O, orthorhombic, P212121 (no. 19), a = 5.4475(3) Å, b = 12.2779(7) Å, c = 18.0975(11) Å, V = 1210.43(12) Å3, Z = 4, Rgt(F) = 0.0326, wRref(F2) = 0.0855, T = 100 K.