Nadia S. El-Gohary

Synthesis, Antimicrobial, Antiquorum-Sensing, and Cytotoxic Activities of New Series of Isoindoline-1,3-dione, Pyrazolo[5,1-a]isoindole, and Pyridine Derivatives

New series of isoindoline‐1,3‐diones 2–9, pyrazolo[5,1‐a]isoindoles 10–14, and pyridines 16–18 were synthesized. Twenty of the synthesized compounds were screened for their antibacterial activity against S. aureus, B. cereus, and E. coli. Compound 5 was proved to be the most active member in this study, showing the highest antibacterial activity against the three selected microorganisms. The antifungal activity of these compounds was also tested against C. albicans and A. flavus 3375. Compounds 4, 5, 8, and 17a exhibited the best antifungal activity against A. flavus 3375. The same compounds were examined for their antiquorum‐sensing activity against Ch. violacium ATCC 12472, whereas compound 5 displayed strong antiquorum‐sensing activity. The in vitro cytotoxicity testing of compounds 4–9 and 17a against human normal lung fibroblast (W138) cell line revealed that compounds 4, 5, and 8 are the least cytotoxic analogs in this study. In vivo acute toxicity testing of compounds 4, 5, and 8 was performed. The DNA‐binding affinity of compounds 4–9 and 17a was also tested and the obtained results showed that all tested compounds have moderate DNA‐binding affinity.

Antimicrobial and antiquorum-sensing studies. Part 2: synthesis, antimicrobial, antiquorum-sensing and cytotoxic activities of new series of fused [1,3,4]thiadiazole and [1,3]benzothiazole derivatives

New series of [1,3,4]thiadiazolo[3,2-a]pyrimidines, [1,3,4]thiadiazolo[2,3-b]quinazolines, and pyrimido[2,1-b][1,3]benzothiazoles have been synthesized and characterized by analytical and spectrometrical methods (IR, MS, 1H, and 13C NMR). Sixteen of the synthesized compounds; namely, 3a, b, 5a–f, 8a, b, 10, 11a–c, and 13a, b were screened for antibacterial activity against Escherichia coli, Staphylococcus aureus, and Bacillus cereus. They were found to be either moderately active, slightly active or inactive against the selected microorganisms. The antifungal activity of these compounds were also tested against Candida albicans, Aspergillus fumigatus 293, and Aspergillus flavus 3375. Compound 11a showed potent antifungal activity against the three selected fungi; the rest of the tested compounds displayed either weaker activity or were completely inactive. The same compounds were examined for antiquorum-sensing activity against Chromobacterium violaceum ATCC 12472, where compounds 3a, 10, 11a, and 13a, b exhibited promising activity. The in vitro cytotoxic activity of these compounds was also studied by brine shrimp lethality bioassay, and results indicated that compounds 3a, 11a, and 13a have the highest cytotoxic activity.

Synthesis and in vitro antitumor activity of new quinoline, pyrimido[4,5-b]quinoline, [1,2,3]triazino[4,5-b]quinoline, and [1,2,4]triazolo[2′,3′:3,4]pyrimido[6,5-b]quinoline analogs

New series of quinoline, pyrimido[4,5-b]quinoline, [1,2,3]triazino[4,5-b]quinoline, and [1,2,4]triazolo[2′,3′:3,4]pyrimido[6,5-b]quinoline analogs have been synthesized and characterized by analytical and spectrometrical methods (IR, 1H NMR, 13C NMR, MS). Fifteen of the newly synthesized compounds; namely, 3a, b, 4b, 6a, b, 10a–f, and 14a–d were evaluated for their in vitro antitumor activity at the National Cancer Institute (NCI) 60 cell lines panel assay. Compounds 4b and 10f are the most active members in this study, demonstrating significant broad spectrum antitumor activity against most of the tested sub-panel tumor cell lines. The detailed synthesis, spectroscopic, and biological data are described.

Antimicrobial and Antiquorum-Sensing Studies. Part 3: Synthesis and Biological Evaluation of New Series of [1,3,4]Thiadiazoles and Fused [1,3,4]Thiadiazoles

New series of [1,3,4]thiadiazoles and fused [1,3,4]thiadiazoles were synthesized. The newly synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Escherichia coli. Compounds 3b and 10a displayed the highest activity against E. coli with MIC value of 78.125 μg/mL. In addition, compound 10a exhibited the highest activity against B. cereus with MIC value of 156.25 μg/mL. The antifungal activity of these compounds was also tested against Candida albicans and Aspergillus flavus 3375. Compounds 3b, 5a, 10a, and 12b showed the best activity against A. flavus 3375 with MIC value of 19.531 μg/mL. The same compounds were examined for their antiquorum‐sensing activity against Chromobacterium violaceum ATCC 12472, whereas compounds 3b, 5a, and 12b exhibited moderate activity. In vitro cytotoxicity testing of compounds 3b,c, 5a, 6a, 10a, and 12a,b against human normal lung fibroblast (W138) cell line was performed. The in vivo acute toxicity of the same compounds was also tested and the obtained results indicated that compound 10a is the least toxic analog. The same compounds were studied for their DNA‐binding affinity and the obtained results showed that compounds 3b, 10a, and 12a,b have moderate DNA‐binding affinity.

Structure-based drug design and biological evaluation of 2-acetamidobenzothiazole derivative as EGFR kinase inhibitor

Abstract EGFR tyrosine kinase has been reported mainly in 40–80% of non-small lung cancers, in addition to colon and breast cancers. In this study, we illustrate the synthesis of a highly potent antitumor agent. The synthesized compound 4 was screened at NCI, USA, for antitumor activity against non-small lung cancer, colon cancer and breast cancer cell lines. Results indicated that this compound is more potent antitumor agent compared to erlotinib against all tested cell lines except breast cancer (MDA-MB-468) cell line. In addition, it was tested initially at a single dose concentration of 100 µM over 11 different kinases. At this concentration, 94.45% inhibition of the enzymatic activity of EGFR kinase was observed, while the inhibition in activity was below 55% in all other kinases. Compound 4 was further tested in a 10-dose IC50 mode and showed IC50 value of 0.239 µM for EGFR kinase. In vivo acute toxicity of this compound was also tested.

Synthesis and biological screening of new thiazolo[4,5-d]pyrimidine and dithiazolo[3,2-a:5′,4′-e]pyrimidinone derivatives as antimicrobial, antiquorum-sensing and antitumor agents

New thiazolopyrimidine and dithiazolopyrimidinone derivatives 2-11 were synthesized and estimated for antimicrobial activity against S. aureus, B. cereus, E. coli, C. albicans, A. fumigatus and A. terreus. The attained results proved that 4, 8a and 11g have significant effectiveness against S. aureus and B. cereus. On the other hand, 7, 10b, 10c and 11h exhibited prominent activity against B. cereus, whereas 8a, 10b and 11g were proved to be active against E. coli. From another point of view, 4 and 8a exhibited promising efficacy against A. fumigatus and A. terreus; moreover, 8a showed outstanding efficacy against C. albicans. Quorum-sensing inhibitory activity of the new compounds was esteemed against C. violaceum, where 7, 8a, 9b, 10a-c, 11d and 11g have acceptable efficacy. In vitro antitumor efficacy of the same compounds against HepG2, HCT-116 and MCF-7 cancer cell lines was also tested. Compounds 4 and 11h showed enhanced effectiveness against the three cell lines, whereas 10b displayed eminent activity against HCT-116 and MCF-7 cells. Moreover, 11a was found to have outstanding activity against MCF-7 cells, while 11i showed promising efficacy against HepG2 cells. The in vitro active antitumor compounds were evaluated for in vivo antitumor effectiveness against EAC in mice, as well as in vitro cytotoxicity against WI38 and WISH normal cells. Results manifested that 4 has the strongest in vivo activity, and that all investigated analogs are less cytotoxic than 5-FU against both normal cell lines. DNA-binding affinity of the active compounds was examined, where 4, 8a, 10c, 11d and 11g,h displayed strong affinity. In silico studies proved that majority of the analyzed compounds are in conformity with the optimum needs for good oral absorption.

Unfortunately, in the article: Synthesis, Antimicrobial, Antiquorum-Sensing, and Cytotoxic Activities of New Series of Isoindoline-1,3-dione, Pyrazolo[5,1-a]-isoindole, and Pyridine Derivatives

– Page 668, right column, 1st paragraph, 3rd line should read: mmol/mL instead of mM/mL – Page 669, Table 1 should read: MICs, mg/mL (mmol/mL) – Page 669, the 2nd footnote of Table 1 should read: MICs (mmol/mL) are shown between parentheses. – Page 670, Table 3 should read: MICs, mg/mL (mmol/mL) – Page 670, the 2nd footnote of Table 3 should read: MICs (mmol/mL) are shown between parentheses. – Page 670, left column, 1st paragraph, 6th line should read: mmol/mL instead of mM/mL – Page 671, left column, “In vitro cytotoxicity testing”, 5th line should read mmol/mL instead of mM/mL – Page 671, Table 4 should read: IC50 (mmol/mL) instead of IC50 (mM/mL) – Page 678, left column, “In vitro cytotoxicity testing”, 2nd paragraph, 8th line should read: mmol/mL instead of mM/mL Arch. Pharm. Chem. Life Sci. 2015, 348, 835 Archiv der Pharmazie ARCH PHARM