Publications by authors named "Iman A Y Ghannam"

5 Publications

  • Page 1 of 1

Discovery of 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids as novel PPARα agonists with anti-hyperlipidemic and antioxidant activities: Design, synthesis and in vitro/in vivo biological evaluation.

Bioorg Chem 2021 Oct 16;115:105170. Epub 2021 Jul 16.

Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Cairo 12622, Egypt. Electronic address:

In the current work, a series of novel 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids (10a-o) and (11a-e) were synthesized and evaluated as new PPARα agonists in order to find new agents with higher activity and fewer side effects. The 2-propanoic acid derivative 10a and the 2-butanoic acid congener 10i showed the best overall PPARα agonistic activity showing E% values of 50.80 and 90.55%, respectively, and EC values of 8.9 and 25.0 μM, respectively, compared to fenofibric acid with E = 100% and EC = 23.22 μM, respectively. These two compounds also stimulated carnitine palmitoyltransferase 1A gene transcription in HepG2 cells and PPARα protein expression. Molecular docking simulations were performed for the newly synthesized compounds to study their predicted binding pattern and energies in PPARα active site to rationalize their promising activity. In vivo, compounds 10a and 10i elicited a significant hypolipidemic activity improving the lipid profile in triton WR-1339-induced hyperlipidemic rats, including serum triglycerides, total cholesterol, LDL, HDL and VLDL levels. Compound 10i possessed better anti-hyperlipidemic activity than 10a. At a dose of 200 mg/kg, it demonstrated significantly lower TC, TG, LDL and VLDL levels than that of fenofibrate at the same dose with similar HDL levels. Compounds 10i and 10a possessed atherogenic indices (CRR, AC, AI, CRI-II) like that of fenofibrate. Additionally, a promising antioxidant activity indicated by the increased tissue reduced glutathione and plasma total antioxidant capacity with decreased plasma malondialdehyde levels was demonstrated by compounds 10a and 10i. No histopathological alterations were recorded in the hepatic tissue of compound 10i (200 mg/kg).
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http://dx.doi.org/10.1016/j.bioorg.2021.105170DOI Listing
October 2021

Fusarochromene, a novel tryptophan-derived metabolite from .

Org Biomol Chem 2021 01;19(1):182-187

School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.

Fusarochromene isolated from the plant pathogenic fungus, Fusarium sacchari is closely related to a group of mycotoxins including fusarochromanone previously isolated from various Fusaria spp. Despite their assumed polyketide biogenesis, incorporation studies with 13C-labelled acetate, glycerol and tryptophans show that fusarochromene is unexpectedly derived via oxidative cleavage of the aromatic amino acid tryptophan. A putative biosynthetic gene cluster has been identified.
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http://dx.doi.org/10.1039/d0ob02031aDOI Listing
January 2021

Novel 2-arylbenzothiazole DNA gyrase inhibitors: Synthesis, antimicrobial evaluation, QSAR and molecular docking studies.

Bioorg Chem 2019 12 24;93:103373. Epub 2019 Oct 24.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, P.O. Box 11562, Cairo, Egypt; Molecular Modeling Unit, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, P.O. Box 11562, Cairo, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, New Giza University, Newgiza, km 22 Cairo-Alexandria Desert Road, Cairo, Egypt.

A series of new 2-arylbenzothiazole derivatives (4, 5, 6a-j, 7a-i and 8a,b) was synthesized and tested for their antimicrobial activity against different Gram-positive, Gram-negative bacteria and yeast using ciprofloxacin and fluconazole as positive controls for the antibacterial and antifungal activities, respectively. The target compounds showed stronger inhibitory activity against Gram-negative than Gram-positive bacteria. The minimum inhibitory concentration (MIC) values were determined for those compounds showed zone of inhibition ≥ 13 mm. Based on the MIC values for the tested compounds against E. coli, compounds (4, 5, 6c, 6d, 6g, 6i, 6j, 7b, 7c, 7g and 8a) were selected and tested for their E. coli gyrase inhibitory activity. The tested compounds showed moderate inhibitory activity against E. coli gyrase. Compounds 5, 6c, 6i, 6j and 7b displayed high inhibitory activity against E. coli gyrase with IC values below 10 µM, however, they were less active than ciprofloxacin (E. coli gyrase IC = 1.14 µM). The p-hydroxy-m-methoxy benzothiazole analogue 6c was the most active tested compound (E. coli gyrase IC = 4.85 µM). Quantitative structure-activity relationship (QSAR) study was also implemented for the newly synthesized compounds. The QSAR study indicated that the structural feature that governs the anti-microbial activity for the newly synthesized benzothiazole derivatives is their structural hydrophilic-lipophilic balance what agrees with the chemical intuition where this balance governs their cellular absorption and so their antimicrobial activity. Molecular docking showed that the newly synthesized compounds possess the required structural feature for E. coli gyrase B inhibition through interaction with the key amino acids Asp73 and Gly77.
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http://dx.doi.org/10.1016/j.bioorg.2019.103373DOI Listing
December 2019

Design, synthesis, and molecular docking of novel indole scaffold-based VEGFR-2 inhibitors as targeted anticancer agents.

Arch Pharm (Weinheim) 2018 Feb 11;351(2). Epub 2018 Jan 11.

National Research Centre, Pharmaceutical and Drug Industries Research Division, Chemistry of Natural and Microbial Products Department, Cairo, Egypt.

A series of new indole derivatives 1-18 was synthesized and tested for their cytotoxic activity on a panel of 60 tumor cell lines. Additionally, molecular docking was carried out to study their binding pattern and binding affinity in the VEGFR-2 active site using sorafenib as a reference VEGFR-2 inhibitor. Based on the molecular docking results, compounds 5a, 5b, 6, 7, 14b, 18b, and 18c were selected to be evaluated for their VEGFR-2 inhibitory activity. Compound 18b exhibited a broad-spectrum antiproliferative activity on 47 cell lines, with GI % ranging from 31 to 82.5%. Moreover, compound 18b was the most potent VEGFR-2 inhibitor with an IC value of 0.07 μM, which is more potent than that of sorafenib (0.09 μM). A molecular docking study attributed the promising activity of this series to their hydrophobic interaction with the VEGFR-2 binding site hydrophobic side chains and their hydrogen bonding interaction with the key amino acids Glu885 and/or Asp1046.
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http://dx.doi.org/10.1002/ardp.201700299DOI Listing
February 2018

Synthesis, molecular docking study and antitumor activity of novel 2-phenylindole derivatives.

Eur J Med Chem 2012 Jan 11;47(1):387-98. Epub 2011 Nov 11.

Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, El-Bohouth Street, 12622 Dokki, Cairo, Egypt.

The starting material, 4-(1-indol-2-yl)phenol 1 was obtained via Fischer synthesis. Vilsmeir Haack(')s formylation of 1 gave the carboxaldehyde derivative 2 which was subjected to different reactions affording the 3-substituted compounds 3-10. Compound 1 reacted with halo esters to give 11 and 12a,b. The reaction of 12a with various amino derivatives gave compounds 13-16. The hydrazide derivative 15a reacted with 1,3-diketones, ethyl acetoacetate and aromatic carboxylic acid derivatives to give 17a,b, 18 and 19a-e, respectively. Antitumor activity of target compounds were tested against breast cancer cell lines (MCF-7) and (MDA-MB-231). The most potent compound was 3e with IC(50) = 1.60 nM against (MCF-7). Docking was performed on colchicine binding site of tubulin to study the binding mode of the designed compounds.
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http://dx.doi.org/10.1016/j.ejmech.2011.11.007DOI Listing
January 2012
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