Mosaad S. Mohamed

Novel 6,8-dibromo-4(3H)quinazolinone derivatives of anti-bacterial and anti-fungal activities

Starting from 4-(6,8-dibromo-2-phenyl-4-oxo-(4H)-quinazolin-3-yl)-benzoic acid ethyl ester (II) and its acid hydrazide III, a new series of Schiff bases IV and their cyclized products, thiazolidinones V, oxadiazole VIII, pyrazoles X-XII, pyrroles XIII-XV and other related products were synthesized. These compounds were screened for their anti-bacterial activity against Gram-positive bacteria (Staphylococcus aureus, Legionella monocytogenes and Bacillus cereus) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium) and anti-fungal activity (Candida albicans and Aspergillus flavus) using paper disc diffusion technique. The minimum inhibitory concentrations (MICs) of the compounds were also determined by agar streak dilution method. Among the synthesized compounds 2-(4-(2-phenyl-6,8-dibromo-4-oxo-(4H)quinazolin-3-yl)-N-ethylamido benzoic acid hydrazide VIIa was found to exhibits the most potent in vitro anti-microbial activity with the MICs of 1.56, 3.125, 1.56, 25, 25 and 25 microg/ml against E. coli, S. typhimurium, L. monocytogenes, S. aureus, P. aeruginosa, and B. cereus respectively. Compound 2-(4-(2-phenyl-6,8-dibromo-4-oxo-(4H)quinazolin-3-yl)-N-methyl thioamido benzoic acid hydrazide VIIc was found to exhibit the most potent in vitro anti-fungal activity with MICs 0.78 and 0.097 microg/ml against C. albicans and A. flavus.

Synthesis and biological evaluation of some thio containing pyrrolo [2,3-d]pyrimidine derivatives for their anti-inflammatory and anti-microbial activities.

The pyrroles Ia-c were used as precursor for the preparation of pyrrolo [2, 3-d] pyrimidine-2 and/or 4 thione derivatives IIa-f. A series of 8-Aryl-pyrrolo [2, 3-d] thiazolo[3,2-a]pyrimidine VI and VII were prepared. Alkylation of the thione compounds in basic medium afforded the pyrrolo [2, 3-d] pyrimidine IV. Also, some 2-amino pyrrolo [2, 3-d]pyrimidines V were obtained. Some newly synthesized compounds were examined for their in vitro anti-inflammatory. Also, all new compounds were examined for their in vivo anti-microbial activity. Several derivatives, showed a promising anti-inflammatory activity in compared to ibuprofen. In this paper, we examine and discuss the structure-activity relationships and anti-inflammatory activities of these compounds.

Synthesis and kinetic testing of new inhibitors for a metallo-β-lactamase from Klebsiella pneumonia and Pseudomonas aeruginosa

There are currently no clinically useful inhibitors against metallo-β-lactamases (MBLs), enzymes that confer resistance against a broad spectrum of commonly used antibiotics and that are produced by an increasing number of bacterial pathogens. New pyrrole derivatives were synthesized and assayed for their inhibitory effect on the catalytic activity of the IMP-1 MBL from Pseudomonas aeruginosa and Klebsiella pneumoniae. Six compounds tested (3a-3c, 5, 7 and 8) show micromolar inhibition constants (K(i) values range from ∼10 to 30 μM). In silico docking was employed to investigate the binding mode of the strongest inhibitor, 3b, in the active site of IMP-1. Implications for further improvements of binding efficiency and specificity are discussed.

Synthesis of certain pyrrole derivatives as antimicrobial agents

Synthesis of certain pyrrole derivatives as antimicro-bial agents In an effort to establish new pyrroles and pyrrolo[2,3-d] pyrimidines with improved antimicrobial activity we report here the synthesis and in vitro microbiological evaluation of a series of pyrrole derivatives. A series of new 2-aminopyrrole-3-carbonitriles (1a-d) were synthesized from the reaction of benzoin, primary aromatic amines and malononitrile, from which a number of pyrrole derivatives (2a-d to 5a-d) and pyrrolo[2,3-d]pyrimidines (6a-d to 10a, d) were synthesized. The in vitro antimicrobial testing of the synthesized compounds was carried out against Gram-positive, Gram-negative bacteria and fungi. Some of the prepared compounds, [2-amino-1-(2-methylphenyl)-4,5-diphenyl-1H-pyrrole-3-carbonitriles (1b), 2-amino-3-carbamoyl-1-(3-methylphenyl)-4,5-diphenyl-1H-pyrroles (2b), N-(3-cyano-1-(2-methylphenyl)-4,5-diphenyl-1H-pyrrol-2-yl)-acetamides (3b), N-(3-cyano-1-(3-methylphenyl)-4,5-diphenyl-1H-pyrrol-2-yl)-acetamides (3c), 2-amino-1-(4-methoxyphenyl)-4,5-diphenyl-3-tetrazolo-1H-pyrroles (5d), 7-(4-methoxyphenyl)-5,6-diphenyl-7H-pyrrolo [2,3-d]pyrimidin-4(3H)-ones (7d), 7-(3-methylphenyl)-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4(3H)-thione (9b) and N-(7-(2-methylphenyl)-5,6-diphenyl-7H-pyrrolo[2,3-d] pyrimidine)-N-aryl amines (10a)] showed potent antimicrobial activity. Sinteza derivata pirola kao antimikrobnih tvari U radu je opisana sinteza novih derivata pirola i pirolo[2,3-d]pirimidina s poboljšanim antimikrobnim djelovanjem. Reakcijom benzoina, primarnih aromatskih amina i malononitrila sintetizirana je serija novih 2-aminopirol-3-karbonitrila (1a-d), iz kojih su potom pripravljeni derivati pirola (2a-d do 5a-d) i pirolo[2,3-d]pirimidina (6a-d do 10a, d). Sintetiziranim spojevima ispitano je in vitro antimikrobno djelovanje na različite Gram-pozitivne, Gram-negativne bakterije i gljivice. Neki od sintetiziranih spojeva [2-amino-1-(2-metilfenil)-4,5-difenil-1H-pirol-3-karbonitril (1b), 2-amino-3-karbamoil-1-(3-metilfenil)-4,5-difenil-1H-pirol (2b), N-(3-cijano-1-(2-metilfenil)-4,5-difenil-1H-pirol-2-il)-acetamid (3b), N-(3-cijano-1-(3-metilfenil)-4,5-difenil-1H-pirol-2-il)-acetamid (3c), 2-amino-1-(4-metoksifenil)-4,5-difenil-3-tetrazolo-1H-pirol (5d), 7-(4-metoksifenil)-5,6-difenil-7H-pirolo[2,3-d]pirimidin-4(3H)-on (7d), 7(3-metilfenil)-5,6-difenil-7H-pirolo[2,3-d]pirimidin-4(3H)-tion (9b) i N-(7-(2-metilfenil)-5,6-difenil-7H-pirolo[2,3-d]pirimidin)-N-aril amin (10a)] imaju snažno antimikrobno djelovanje.

Synthesis of Certain Pyrimidine Derivatives as Antimicrobial Agents and Anti-Inflammatory Agents

A variety of novel bicyclic and tricyclic pyrimidine derivatives was obtained via reaction of 6-amino-2-thioxo-1H-pyrimidine-4-one (1) with a different reagents. The antimicrobial and anti-inflammatory activities of some of the synthesized compounds were tested.

Synthesis of new 2-thiouracil-5-sulphonamide derivatives with antibacterial and antifungal activity

Abstract2-Thiouracil-5-sulphonic acidN-(4-acetylphenyl) Amide (1) was reacted with a series of aromatic aldehydes giving chalcones2 (Claisen-Schemidt reaction), some of these chalcones were reacted with urea and thiourea giving pyrimidine-2-one and pyrimidine-2 thione derivatives respectively of the type3a,b and4a,b. In addition many chalcones were reacted with hydroxylamine hydrochloride giving isoxazoline derivatives5a,b. They could also reacted with Phenylhydrazine to give pyrazoline derivatives6a,b, chalcones also were reacted withethylcyano acetate and/or malononitryl in pyridine giving pyran derivatives7a,c and8a,c In another pathway chalcones were epoxidised by H2O2 giving epoxides9a,c which in turn were reacted with Phenylhydrazine giving 4-hydroxypyrazoline derivatives10a,c. In another reaction chalcones were reacted with ethylcyanoacetate in presence of amm.acetate giving pyridone derivatives11a,d which could be prepared also in exellent yield from compound 1 by its reaction with certain aromatic aldehydes and ethylcyanoacetate in presence of ammonium acetate. Finally, compound 1 was reacted with semicarbazide giving semicarbazone intermediate12 which in turn was reacted with thionyl chloride giving thiadiazole derivative13. The biological effects of some of the new synthesized compounds were also investigated.

Synthesis and kinetic testing of tetrahydropyrimidine-2-thione and pyrrole derivatives as inhibitors of the metallo-β-lactamase from Klebsiella pneumonia and Pseudomonas aeruginosa

Metallo‐β‐lactamases (MBLs), produced by an increasing number of bacterial pathogens, facilitate the hydrolysis of many commonly used β‐lactam antibiotics. There are no clinically useful antagonists against MBLs. Two sets of tetrahydropyrimidine‐2‐thione and pyrrole derivatives were synthesized and assayed for their inhibitory effects on the catalytic activity of the IMP‐1 MBL from Pseudomonas aeruginosa and Klebsiella pneumoniae. Nine compounds tested (1a, 3b, 5c, 6b, 7a, 8a, 11c, 13a, and 16a) showed micromolar inhibition constants (Ki values range from ∼20–80 μm). Compounds 1c, 2b, and 15a showed only weak inhibition. In silico docking was employed to investigate the binding mode of each enantiomer of the strongest inhibitor, 5c (Ki = 19 ± 9 μm), as well as 7a (Ki = 21 ± 10 μm), the strongest inhibitor of the pyrrole series, in the active site of IMP‐1.

New condensed pyrroles of potential biological interest: Syntheses and structure–activity relationship studies

The Pyrrole derivatives Ia-d were prepared and utilized for the preparation of pyrrolo[2,3-d]pyrimidine derivatives IIa-c, III, IVa-e, V and VIIIa-c; pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidine VI and pyrrolo[4,3e][1,2,4]triazolo[1,5-c]pyrimidine derivative derivatives VIIa-c. These some newly synthesized compounds were examined for their in vitro antimicrobial activity and in vivo anti-inflammatory. Result indicated that these compounds showed promising anti-inflammatory activity in comparison to ibuprofen (the standard anti-inflammatory drug). The structure-activity relationships (SAR) and anti-inflammatory activities of these compounds are also discussed in this paper.

Synthesis of new 2-thiouracil-5-sulfonamide derivatives with biological activity

Abstract2-Thiouracil-5-sulfonylchloride1 reacted with a series of aromatic and heterocyclic amines to give2a-j. The same compound1 was reacted with a series of sulphonamides giving different sulphonamides of type3a-e. On the other hand compound1 was allowed to react with p-aminoacetophenone givining compound4 which in turn was allowed to react with derivatives of alkyl thiosemicarbazides to give thiosemicarbazones of type5a-e, also compound4 was monobrominated to give compound6 which in turn was reacted thiosemicarbazones of some aldehydes to give the corresponding thiazole derivatives7a-f. In the same time compound4 was reacted with a series of aromatic and heterocyclic aldehydes givining chalcones8a-g (Claisen-Schemidt reaction). Also compound4 was allowed to react with a series of aromatic and heterocyclic aldehydes, ethyl cyano acetate and/or malononitrile, and ammonium acetate giving pyridine derivatives9a-d and10a-e respectively. The biological effects of some of the new synthesized compounds was also investigated.

Evaluation of the anti-inflammatory activity of some pyrrolo[2,3-d]pyrimidine derivatives

A series of novel pyrrolo[2,3-d]pyrimidine and fused pyrrolo[2,3-d]pyrimidine derivatives were synthesized and their structures were characterized by elemental analysis, 1H NMR, IR, and mass spectroscopy. Their in vivo anti-inflammatory activities were evaluated, and the results indicated that some of the title compounds compounds showed significant activities. These compounds are 2b ((7-(4-Methoxyphenyl)-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-hydrazine), 7b (4-(2-(Benzyl)hydrazinyl)-7-(4-methoxyphenyl)-5,6-diphenyl-7H-pyrrolo[2,3-d] pyrimidine), 7d (4-(2-(Benzyl)hydrazinyl)-7-(4-methoxyphenyl)-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine), and 9b (4-(3,5-Dimethyl-4H-pyrazol-1-yl)-7-(4-Methoxyphenyl)-5,6-diphenyl-4,7dihydro-3H-pyrrolo[2,3-d]pyrimidine).