Mastoura M. Edrees

Antimicrobial, antitumor and 5α-reductase inhibitor activities of some hydrazonoyl substituted pyrimidinones.

A series of 2-[N-aryl-2-oxo-2-(4-chlorophenyl)ethanehydrazonoyl]-6-methyl-4(3H)-pyrimidinones 5 were prepared by coupling the diazonium salt of aniline derivatives with 2-(4-chlorobenzoylmethylene)-6-methyl-4(3H)-pyrimidinone 4 in sodium hydroxide solution. The structures of these newly synthesized compounds were confirmed by IR, NMR, mass spectrometry and elemental analyses and the tautomeric structure of these compounds was discussed. All the newly synthesized compounds were screened for their antibacterial and antifungal activities, some of which exhibited moderate activity. Also, the above compounds were evaluated for their antitumor activity against a panel of 60 human tumor cell lines by the National Cancer Institute (NCI), USA. Compounds 5b, 5d and 5i showed good cytotoxic activities against the tested cell lines. In addition, the newly synthesized compounds were screened for their 5α-reductase inhibitor activity and all the tested compounds showed activities in descending order as follows 5b, 5c, 5g, 5j, 5d, 5h, 5f, 5e and 5i.

CG base pair recognition within DNA triple helices by modified N-methylpyrrolo-dC nucleosides

3-Aminophenyl-modified analogues of the bicyclic nucleoside N-methyl-3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one were synthesised and incorporated directly into triplex-forming oligonucleotides in order to utilise their extended hydrogen bonding motif for recognition of the CG base pair. All analogues demonstrated strong binding affinity and very good selectivity for CG from pH 6.2 to 7.0; a marked improvement on previous modifications.

Heterocyclisation of 2,5-diacetyl-3,4-disubstituted-thieno[2,3- b ]thiophene bis-thiosemicarbazones leading to bis-thiazoles and bis-1,3,4-thiadiazoles as anti-breast cancer agents

In this paper, the synthesis of bis-thiazoles and bis-1,3,4-thiadiazoles linked to a thienothiophene nucleus is described. The synthesis was achieved through interaction between 2,5-diacetylthieno[2,3-b]thiophene bis-thiosemicarbazones with a variety of hydrazonyl halides in a basic medium. All the synthesised compounds were characterised by IR, 1H NMR, 13C NMR and mass spectroscopic analyses. The newly synthesised compounds represent a variety of novel polyheteroatomic moieties containing nitrogen and sulfur. Most of the synthesised compounds were evaluated for their antitumour activity against the breast cancer MCF-7 cell line. The results revealed that four compounds are equipotent to tamoxifen (IC50 = 8.04 μg mL−1) with IC50 = 8.23, 8.26, 8.68 and 9.12 μg mL−1 respectively.

Synthesis and Characterization of Some New Bis-Pyrazolyl-Thiazoles Incorporating the Thiophene Moiety as Potent Anti-Tumor Agents

A new series of 1,4-bis(1-(5-(aryldiazenyl)thiazol-2-yl)-5-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-3-yl)benzenes 3a–i were synthesized via reaction of 5,5′-(1,4-phenylene)bis(3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamide) (1) with hydrazonoyl halides 2a–i. In addition, reaction of 1 with ethyl chloroacetate afforded bis-thiazolone derivative 8 as the end product. Reaction of compound 8 with methyl glyoxalate gave bis-thiazolone derivative 10. The structures of the newly synthesized compounds were established on the basis of spectroscopic evidences and their alternative syntheses. All the synthesized compounds were evaluated for their anti-tumor activities against hepatocellular carcinoma (HepG2) cell lines, and the results revealed promising activities of compounds 3g, 5e, 3e, 10, 5f, 3i, and 3f with IC50 equal 1.37 ± 0.15, 1.41 ± 0.17, 1.62 ± 0.20, 1.86 ± 0.20, 1.93 ± 0.08, 2.03 ± 0.25, and 2.09 ± 0.19 μM, respectively.

Synthesis and Characterization of Some Substituted 3, 4-dihydronaphthalene Derivatives through Different Enaminones as Potent Cytotoxic Agents

A new series of novel substituted 3,4-dihydronaphthalene incorporated to benzo[h]quinoline, benzo[g]indazole, thiazolidin-4-one, pyrazolo[3,4-d]thiazol and thiazolo[4,5-b]pyridine ring systems were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines. Some of the tested compounds exhibited promising carcinoma growth inhibition. The detailed synthesis, spectroscopic data and biological activities of the tested compounds were reported.

Synthesis, tautomeric structure and antimicrobial activity of 3-arylhydrazono-4-phenyl-[1,2,4]-triazepino[2,3-a]quinazoline-2,7(1H)-diones.

A simple strategy for the synthesis of the hitherto unreported 3-arylazo-4-phenyl- [1,2,4]triazepino[2,3-a]quinazoline-2,7(1H)-diones is described. Spectral data indicated that the studied compounds exist predominantly in the hydrazone tautomeric form. The antimicrobial activity of the newly synthesized compounds was also evaluated. The results indicated that some of these compounds have moderate activity towards bacteria.

Microwave-assisted one pot three-component synthesis of some novel pyrazole scaffolds as potent anticancer agents

BackgroundPyrazoles, thiazoles and 1,3,4-thiadiazoles have been reported to possess various pharmacological activities.ResultsAn efficient and a novel approach for the synthesis of some novel pyrazole based-azoles are described via multi-component reaction under controlled microwave heating conditions. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, 1H NMR and mass spectral data. All the synthesized compounds were tested for in vitro activities against two antitumor cell lines, human lung cancer and human hepatocellular carcinoma compared with the employed standard antitumor drug (cisplatin).ConclusionsAll the newly synthesized compounds were evaluated for their anticancer activity against human lung cancer and human hepatocellular carcinoma cell lines using MTT assay. The results obtained exploring the high potency of six of the tested compounds compared with cisplatin. Graphical abstractMicrowave-assisted one pot three-component synthesis of some novel pyrazole scaffolds as potent anticancer agents

Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles

A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. Most of the synthesized compounds were tested for in vitro activity against human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) cell lines compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 8, 4e and 7b have promising activities against the A-549 cell line (IC50 values of 2.78 ± 0.86 μg/mL, 5.37 ± 0.95 μg/mL and 5.70 ± 0.91 μg/mL, respectively) while compound 7b has promising activity against the HepG-2 cell lines (IC50 = 3.54 ± 1.11 μg/mL). Moreover, computational studies using MOE 2014.09 software supported the biological activity results.

Molecular modeling study bioactive natural product of khellin analogues as a novel potential pharmacophore of EGFR inhibitors

Khelline is naturally occurring furochromone exhibited significant Epidermal Growth Factor Receptor (EGFR) inhibitory activity. The newly synthesized compounds 2–5 displayed the most potent EGFR inhibitory activity on MCF-7 and HeLa. In vitro study against 59 different human tumour cell lines derived from nine cancer type in NCI (USA), which was presented and documented. Molecular docking simulation was performed to position compounds 1–5 into the EGFR active site to determine the probable binding mode.

5-(Thiophen-2-yl)-1,3,4-thiadiazole derivatives: synthesis, molecular docking and in vitro cytotoxicity evaluation as potential anticancer agents

Background Nowadays, cancer is an important public health problem in all countries. Limitations of current chemotherapy for neoplastic diseases such as severe adverse reactions and tumor resistance to the chemotherapeutic drugs have been led to a temptation for focusing on the discovery and development of new compounds with potential anticancer activity. The importance of thiophene and thiadiazole rings as scaffolds present in a wide range of therapeutic agents has been well reported and has driven the synthesis of a large number of novel antitumor agents. Methods A series of new 1,3,4-thiadiazoles were synthesized by heterocyclization of N-(4-nitrophenyl)thiophene-2-carbohydrazonoyl chloride with a variety of hydrazine-carbodithioate derivatives. The mechanisms of these reactions were discussed and the structure of the new products was elucidated via spectral data and elemental analysis. All the new synthesized compounds were investigated for in vitro activities against human hepatocellular carcinoma (HepG-2) and human lung cancer (A-549) cell lines compared with cisplatin standard anticancer drug. Moreover, molecular docking using MOE 2014.09 software was also carried out for the high potent compound 20b with the binding site of dihydrofolate reductase (DHFR, PDB ID (3NU0)). Results The results showed that compound 20b has promising activities against HepG-2 and A-549 cell lines (IC50 value of 4.37±0.7 and 8.03±0.5 μM, respectively) and the results of molecular docking supported the biological activity with total binding energy equals −1.6 E (Kcal/mol). Conclusion Overall, we synthesized a new series of 1,3,4-thiadiazoles as potential antitumor agents against HepG-2 and A-549 cell lines.