Dalia H. Soliman

New quinoxaline 1, 4-di-N-oxides: Anticancer and hypoxia-selective therapeutic agents

A new series of quinoxaline 1,4-di-N-oxides was synthesized and evaluated for antitumor and hypoxic-selective cytotoxic activities. Antitumor activity against liver carcinoma (Hepg2) and brain tumor (U251) human cell lines were evaluated, among the tested compounds, 5b and 9b exhibited potential cytotoxic effect against Hepg2 with IC50 values of 0.77 and 0.50 microg/mL respectively, whereas, all the tested compounds lack antitumor activity against U251 human cell line. Moreover, compound 4 was the most potent hypoxia selective-cytotoxin on EAC cell line; IC50 2.5 microg/mL, potency 22 microg/mL, and was approximately 5.4-times more selective cytotoxin (HCR>40) than 3-amino-2-quinoxalinecarbonitrile1,4-dioxide (standard, HCR>7.4). Compounds 8b and 9b were more selective than the standard.

Synthesis, Biological Evaluation and 2D-QSAR Study of Halophenyl Bis-Hydrazones as Antimicrobial and Antitubercular Agents

In continuation of our endeavor towards the development of potent and effective antimicrobial agents, three series of halophenyl bis-hydrazones (14a–n, 16a–d, 17a and 17b) were synthesized and evaluated for their potential antibacterial, antifungal and antimycobacterial activities. These efforts led to the identification of five molecules 14c, 14g, 16b, 17a and 17b (MIC range from 0.12 to 7.81 μg/mL) with broad antimicrobial activity against Mycobacterium tuberculosis; Aspergillus fumigates; Gram positive bacteria, Staphylococcus aureus, Streptococcus pneumonia, and Bacillis subtilis; and Gram negative bacteria, Salmonella typhimurium, Klebsiella pneumonia, and Escherichia coli. Three of the most active compounds, 16b, 17a and 17b, were also devoid of apparent cytotoxicity to lung cancer cell line A549. Amphotericin B and ciprofloxacin were used as references for antifungal and antibacterial screening, while isoniazid and pyrazinamide were used as references for antimycobacterial activity. Furthermore, three Quantitative Structure Activity Relationship (QSAR) models were built to explore the structural requirements controlling the different activities of the prepared bis-hydrazones.

Synthesis, in Vitro and in Silico Studies of Some Novel 5-Nitrofuran-2-yl Hydrazones as Antimicrobial and Antitubercular Agents

In this study, we synthesized two series of novel 5-nitrofuran-2-carbohydrazides 21a-h and 22a-e in addition to a third series of thiophene-2-carbohydrazides 23a-g to develop potent antimicrobial and/or antitubercular agents. The newly synthesized compounds were evaluated in vitro for their antimicrobial and antimycobacterial activities. Most of the 5-nitrofuran-2-carbohydrazides 21a-h and 22a-e displayed variable activity against Aspergillus fumigates, Staphylococcus aureus, Streptococcus pneumonia, Bacillis subtilis, Salmonella typhimurium, Klebsiella pneumonia, Escherichia coli and Mycobacterium tuberculosis. The sulfonamide derivative 21f exhibited superior potency and broad-spectrum antimicrobial activity with minimum inhibitory concentration (MIC)=0.06-0.98 µg/mL and antimycobacterial activity with MIC=3.9 µg/mL. The 5-nitrofuran-2-carbohydrazides 21a, b, g, h and 22a-c exhibited significant antibacterial activity with MIC values in the range of 0.12-7.81 µg/mL. The significances of the 5-nitrofuran moiety and sulfonamide function were explored via the structure-activity relationship (SAR) study. In addition, docking studies revealed that the p-amino benzoic acid (PABA) and binding pockets of the dihydropteroate synthase (DHPS) were successfully occupied by compound 21f. Furthermore, two quantitative structure-activity relationship (QSAR) models were built to explore the structural requirements which controlled the activity.

Design, synthesis and evaluation of novel diaryl pyrrolopyrimidine and pyrrolothiazine derivatives as inhibitors of tumor necrosis factor stimulated gene-14 (TSG-14) production

A novel series of pyrrolothiazines 2-4 and pyrrolopyrimidines 5-7 have been synthesized. The structures of these compounds were established by spectroscopic and element microanalytical data. The newly synthesized compounds were evaluated as inhibitors of TSG-14. The most effective results were obtained by the S-sec-butyl derivatives 6e (80%) and the N-ethyl derivatives 4e (70%).

Three-dimensional quantitative structure activity relationship (QSAR) of cytotoxic active 3,5-diaryl-4,5-dihydropyrazole analogs: a comparative molecular field analysis (CoMFA) revisited study.

In vitro antitumor evaluation of the synthesized 46 compounds of 3,5-diaryl-4,5-dihydropyrazoles against EAC cell lines and 3D QSAR study using pharmacophore and Comparative Molecular Field Analysis (CoMFA) methods were described. CoMFA derived QSAR model shows a good conventional squared correlation coefficient r2 and cross validated correlation coefficient r2cv 0.896 and 0.568 respectively. In this analysis steric and electrostatic field contribute to the QSAR equation by 70% and 30% respectively, suggesting that variation in biological activity of the compounds is dominated by differences in steric (van der Waals) interactions. To visualize the CoMFA steric and electrostatic field from partial least squares (PLS) analysis, contour maps are plotted as percentage contribution to the QSAR equation and are associated with the differences in biological activity.BackgroundPyrazole derivatives exhibit a wide range of biological properties including promising antitumor activity. Furthermore, Aldol condensation assisted organic synthesis has delivered rapid routes to N-containing heterocycles, including pyrazoles. Combining these features, the use of chalconisation-assisted processes will provide rapid access to a targeted dihydropyrazoles library bearing a hydrazino 3D QSAR study using pharmacophore and Comparative Molecular Field Analysis (CoMFA) methods were described for evaluation of antioxidant properties.ResultsChalcones promoted 1 of the 2 steps in a rapid, convergent synthesis of a small library of hydrazinyl pyrazole derivatives, all of which exhibited significant antitumor activity against Ehrlich Ascites Carcinoma (EAC) human tumor cell line comparable to that of the natural anticancer doxorubicin, as a reference standard during this study. In order to understand the observed pharmacological properties, quantitative structure-activity relationship (3D QSAR) study was initiated.ConclusionsChalcones heating provides a rapid and expedient route to a series of pyrazoles to investigate their chracterization scavenging properties. Given their favorable properties, in comparison with known anticancer, these pyrazole derivatives are promising leads for further development and optimization.