Nargues S. Habib

Synthesis of thiazolo[4,5-d]pyrimidine derivatives as potential antimicrobial agents.

In this study, we report the synthesis and antimicrobial evaluation of several new thiazolo[4,5-d] pyrimidine derivatives, namely 7-substituted amino-5-methyl-3-phenylthiazolo[4,5-d]pyrimi-dine-2 (3H)-thiones4a- e,8,13,15, ethyl 2-cyano-2-(7-substituted-5-methyl-3-phenylthiazolo [4,5-d]-pyrimidin-2(3H)-ylidene)acetates5a- b, 2-(7-substituted-5-methyl-3-phenylthiazolo[4,5-d] pyrimidin-2(3H)-ylidene)malononitriles6a- b, 5-methyl-7-morpholino-3-phenylthiazolo[4,5-d] pyrimidine-2(3H)-one 7, and 7-[4-(1-substituted-5-phenyl-4,5-dihydro-1H-pyrazolin-3-yl)anilino]-5-methyl-3-phenylthiazolo[4,5-d]pyrimidine-2(3H)-thiones10- 12. Some of the tested compounds were more active againstC. albicans thanE. coli andP. aeruginosa, and all were inactive against S.aureus.

Synthesis, biological evaluation and molecular docking studies of some pyrimidine derivatives.

Some novel pyrimidine-5-carbonitrile derivatives bearing various substituent have been synthesized. The structures of target compounds were confirmed by elemental analysis and spectral data. Some selected members of the newly synthesized compounds were investigated for their cytotoxic potency against certain human tumor cell lines. Five representative active anticancer compounds 6a, 6c, 6d, 17a and 18a were subjected to docking using MOE program on the 3D structure of two enzymes, namely; thymidylate synthase and dihydrofolate reductase. The antimicrobial activities of the synthesized compounds were tested against Staphylococcus aureus, Pseudomonas aeruginosa, Shigella flexneri and Candida albicans. Compounds 2c, 7a and 9c showed broad spectrum antimicrobial activity.

Design, synthesis and biological evaluation of novel 1,2,4-triazolo and 1,2,4-triazino[4,3-a]quinoxalines as potential anticancer and antimicrobial agents

In an effort to find new leads as anticancer or antimicrobial agents, the present work deals with the synthesis of some novel 1-substituted 1,2,4-triazolo[4,3-a]quinoxalines 7, 9a,b, and 14–19 and 1,2,4-triazino[4,3-a]quinoxalines 10a–c as well as 2-[5-amino-3-(4-chlorophenyl)pyrazol-1-yl]-3-benzylquinoxaline 13. These were synthesized using the key intermediate 3-benzyl-2-hydrazinoquinoxaline 6 with various reagents. Ten compounds, namely 7, 9a, 10b, 11, and 13–18 were chosen by the National Cancer Institute of Bethesda (NCI) for evaluation of their anticancer activity. The results indicated that 9a was the most active and was further evaluated for in vitro five dose assay against 60 human cell lines. It was proven to possess the highest broad spectrum anticancer activity. It showed particular effectiveness towards leukemia SR, non-small cell lung cancer HOP-92, NCI-H460, colon cancer HCT-116, HCT-15, CNS cancer U251, melanoma LOX IMVI, renal cancer A498, prostate cancer PC-3, and breast cancer MDA-MB-468 cell lines (GI50 = 3.91, 3.45, 3.49, 3.21, 1.96, 5.18, 3.69, 1.80, 5.19, and 5.55 μM, respectively). All new compounds were screened for their antimicrobial activity and were very active against P. aeruginosa. Compounds 10a and 16 were twice as active as ampicillin against P. aeruginosa. Five compounds, 9a, b, 10b, 13, and 14 were equipotent to ampicillin against P. aeruginosa. In addition, compound 16 showed a broad spectrum antimicrobial activity. Furthermore, compound 9a showed dual activity as an anticancer and antimicrobial agent.

Synthesis of Some Triazolophthalazine Derivatives for Their Anti-Inflammatory and Antimicrobial Activities

Several novel series of triazolophthalazine derivatives namely; pyrazolylethenyltriazolophthalazinones (4a–d), styryltriazolophthalazinones (5a,b), aryloxopropenyltriazolophthalazinones (7a,b), pyrazolinyl‐ (8a,b), (9a,b) and (10a–f), pyrazolyl‐ (11a–d), (1,2‐oxazol‐5‐yl)‐1,2,4‐triazolo[3,4‐a]phthalazin‐6(5H)‐ones (14a,b), triazolo[3,4‐a]phthalazin‐3‐yl‐pyridine‐3‐carbonitriles (12a,b), triazolo[3,4‐a]phthalazin‐3‐yl)ethylthioacetic acids (13a,b) and 2‐aryl‐5‐arylamino‐1H,5H‐pyrazolo[2″,3″‐1′,5′]imidazo[3′,4′‐1,5]‐1,2,4‐triazolo[3,4‐a]phthalazin‐12(13H)‐ones (15a–c) have been synthesized. The anti‐inflammatory activity of representative compounds has been studied. Compounds 8b, 10c, 10f, 11b, 12a, 13b, and 15a showed anti‐inflammatory activities comparable to that of the reference standard, indomethacin. They exhibit also minimal ulcerogenic effect relevant to the reference standard and were found to be non‐toxic up to 120 mg/kg orally or up to 75 mg/kg through parenteral route. Concerning the antimicrobial activity; compounds 12b and 13b were found to be equipotent to ampicillin against Staphylococcus aureus, while compounds 10a and 10f were found to be as potent as ampicillin against E. coli, whereas compound 14b exhibited equipotency to clotrimazole against Candida albicans. Compounds 8b, 10f, 11b, 12a, and 13b exhibited, besides their antimicrobial activity, moderate to potent anti‐inflammatory profiles. This represents a fruitful matrix for the development of a new class of dual non‐acidic anti‐inflammatory/antimicrobial agents.

Synthesis and biological evaluation of novel series of thieno[2,3-d]pyrimidine derivatives as anticancer and antimicrobial agents

The present study is concerned with the synthesis, anticancer and antimicrobial screening of several new 3-substituted or 2,3-disubstituted-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamide derivatives. Three compounds (4b, 8c, and 11b) were selected by the National Cancer Institute and were first evaluated at a single-dose primary anticancer assay against 60 human cancer cell lines for their in vitro anticancer activity. Compound 8c which passed the criteria for activity in this assay was evaluated against the full panel of 60 human cancer cell lines at five concentrations at tenfold dilutions where it showed non-selective broad-spectrum activity against all cancer cell lines. Furthermore, compounds 4b, 6, 8c, 8d, and 16 showed pronounced antibacterial activities comparable to ampicillin against P. aeruginosa. Therefore, it was concluded that compound 8c may serve as a useful lead compound in search for powerful dual anticancer-antimicrobial agents.

Utility of the Least Squares Method in the PMR Spectrometric Assay of Chloramphenicol and Streptomycin with Their Degradation Products

Abstract The least squares line correlating Id/Is (the ratio between the signal integral values of the drug to the internal reference standard) and concentration was derived and found linear in the range of 10.0–35.0 mg chloramphenicol and 12.0–28.0 mg streptomycin. Each drug was assayed in combination with its degradation product in a ratio of 33 to 300% for the former and 33 to 200% for the latter. Commercial tablets were also assayed for the two components chloramphenicol and streptomycin existing in a ratio 1:1.

Synthesis and Biological Evaluation of Some Novel Thieno[2,3-d] pyrimidine Derivatives as Potential Anti-inflammatory and Analgesic Agents

A novel series of thienopyrimidine derivatives bearing various substituents or linked to various heterocyclic moieties through atoms spacers were prepared starting from 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6- carboxamide potassium salt 3. Twelve out of the prepared compounds were selected and evaluated for their antiinflammatory activity using the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays using diclofenac sodium as a reference standard. The ulcerogenic effects and acute toxicity (ALD50) values of these compounds were also determined. In addition, the analgesic activity of the same compounds was evaluated using the rat tail withdrawal technique. The results revealed that compounds 5a, 13, 14b, 15a, 16a and 16b had high anti-inflammatory effect comparable to diclofenac sodium, whereas compounds 5a, 14a, 15a and 16a revealed pronounced analgesic activity that is equal or higher than that of the reference. All of the tested compounds revealed high GI safety profile and were well tolerated by the experimental animals with high safety margin (ALD50 > 3.0g/Kg).

Synthesis and Benzodiazepine Receptor Binding Activity of 2, 9-Disubstituted Quinolino[2′, 3′-5, 4](3-pyrazolino)[3, 2-b]purin-4-ones

2, 9‐Disubstituted quinolino[2′, 3′‐5, 4](3‐pyrazolino)pyrimidin‐2‐ones and purin‐4‐ones were synthesized and their benzodiazepine receptor activity was evaluated for their ability to displace [3H]R015‐1788 from its specific binding in bovine brain membranes. Compound 5c caused 83 ± 8 %inhibition in [3H]R015‐1788 specific benzodiazepine receptor binding followed by compounds 5f, 5h, and 5i while other analogs were inactive at 10 μM concentration.

Design, synthesis, antibacterial evaluation and molecular docking studies of some new quinoxaline derivatives targeting dihyropteroate synthase enzyme

Development of new antimicrobial agents is a good solution to overcome drug-resistance problems. From this perspective, new quinoxaline derivatives bearing various bioactive heterocyclic moieties (thiadiazoles, oxadiazoles, pyrazoles and thiazoles) were designed and synthesized. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against nine bacterial human pathogenic strains using the disc diffusion assay. In general, most of the synthesized compounds exhibited good antibacterial activities. The thiazolyl 11c displayed significant antibacterial activities against P. aeruginosa (MIC, 12.5 µg/mL vs levofloxacin 12.5 µg/mL). Molecular docking studies indicated that the synthesized compounds could occupy both p-amino benzoic acid (PABA) and pterin binding pockets of the dihydropteroate synthase (DHPS), suggesting that the target compounds could act by the inhibition of bacterial DHPS enzyme. The results provide important information for the future design of more potent antibacterial agents.

Design and Synthesis of Some New 1,2,4- Triazolo[4,3-a]QuinoxalineDerivatives as Potential Antimicrobial Agents

As a part of an ongoing research program to achieve new chemical entities suitable for development as new class of antimicrobial agents, the present work describes the design and synthesis of a new series of substituted-1-methyl- 1,2,4-triazolo[4,3-a]quinoxalines, The newly synthesized compounds were screened for their in vitro antimicrobial activity. The results revealed that the compounds demonstrated significant activity against Gram negative bacteria. Compounds 3 and 11b exhibited twice the activity of ampicillin against Pseudomonas aeruginosa, while compounds 4, 5b, 7, 9a, 10d, 11a, 11c and 12 were equipotent to ampicillin. On the other hand, the tested compounds demonstrated mild antifungal activity. Compound 11d exhibited nearly one-half the activity of clotrimazole against Candida albicans. The structures of the synthesized compounds have been confirmed by elemental analyses, IR, MS, 1H-NMR and 13 C-NMR spectral data.