Publications by authors named "Omaima M AboulWafa"

10 Publications

  • Page 1 of 1

Antiproliferative activity, enzymatic inhibition and apoptosis-promoting effects of benzoxazole-based hybrids on human breast cancer cells.

Bioorg Chem 2021 Apr 20;109:104752. Epub 2021 Feb 20.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, 21521 Alexandria, Egypt. Electronic address:

New benzoxazole derivatives containing 1,3,4-oxadiazole, 1,2,4-triazole or triazolothiadiazine rings were synthesized and screened for their in vitro antiproliferative activities against MCF-7 and MDA-MB-231 breast cancer cell lines using MTT assay. Doxorubicin, cisplatin and 2-(4-aminophenyl)benzothiazole (CJM 126) were used as references. The most active compounds 7a, 8d, 8e and 10c were screened for their antiproliferative activities against MCF-10A normal breast cells where compounds 8e and 7a were the most selective towards MCF-7 and MDA-MB-231 cell lines, respectively compared to CJM 126. In vitro enzymatic inhibition assays of epidermal growth factor receptor (EGFR) and aromatase (ARO) enzymes were performed. Compound 7a showed inhibition of EGFR comparable to that of erlotinib while compound 8e exhibited nearly half the inhibitory activity of erlotinib towards EGFR and was more potent inhibitor of ARO than letrozole. Caspase-9 activation assay, cell cycle analysis and Annexin-V/ Propidium iodide assay performed for compounds 7a, 8d, 8e and 10c demonstrated over expression of caspase-9 protein level, pre G apoptosis and high annexin V binding affinity. Therefore, these compounds are considered as potent apoptosis-promoting agents. The predicted docking studies and in silico chemo-informatic properties of compounds 7a and 8e were appropriate. Compounds 7a and 8e are promising anti-breast cancer agents exhibiting potent apoptosis-promoting properties.
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http://dx.doi.org/10.1016/j.bioorg.2021.104752DOI Listing
April 2021

2-Anilinopyrimidine derivatives: Design, synthesis, in vitro anti-proliferative activity, EGFR and ARO inhibitory activity, cell cycle analysis and molecular docking study.

Bioorg Chem 2020 06 29;99:103798. Epub 2020 Mar 29.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Damanhour, Damanhour, Egypt. Electronic address:

Novel anti-proliferative agents possessing pyrimidine scaffolds were designed, synthesized and evaluated for their IC values using MTT assay. Most compounds displayed good to excellent activity against the two tested breast cancer lines (MCF-7 and MDA-MB-231) as compared to 5-FU. The observed IC values for active compounds ranged from 0.27 to 10.57 µM in MCF-7 compared to the reference drug 5-FU (IC = 10.80 µM) and from 0.73 to 29.07 µM in MDA-MB-231 (IC for 5-FU = 11.40 µM). SAR analysis indicated that compounds 2c, 3b with hydrazone functionalities and compound 12 possessing pyrazolone ring exhibited superior activities. The most promising compounds were evaluated for their inhibitory activity against epidermal growth factor receptor (EGFR) and aromatase (ARO) enzymes and were further tested for caspase-9 activation, apoptosis and Annexin V/PI staining. Results of enzyme-based experiments indicated that the tested compounds 2c and 12 exert their activities through EGFR inhibition while compound 3b exhibited remarkable ARO inhibition activity. Furthermore, they remarkably induce caspase-9 activation and showed pre G1 apoptosis and cell cycle arrest at G2/M phase. In addition, docked compounds displayed good binding affinities to the target enzymes. Binding interaction details for the most promising inhibitors with the active site of the target enzymes EGFR and ARO utilizing MOE-dock method are also reported.
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http://dx.doi.org/10.1016/j.bioorg.2020.103798DOI Listing
June 2020

Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamides.

Molecules 2020 Mar 28;25(7). Epub 2020 Mar 28.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

The preparation of certain 2-(2-oxo-2-chromen-4-yl)--substituted acetamides was planned as a step in the development of new modified nonsteroidal antiestrogens. The purity of target compounds was checked by thin-layer chromatography (TLC), and their structures were confirmed using various spectroscopic tools including IR, H-NMR, C-NMR, and MS spectroscopy. Viability tests were applied using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effect of the synthesized compounds against two breast cancer cell lines, MCF-7 and MDA-MB-231. Compound proved the most active against MCF-7 cells, with an IC value of 0.32 μM. The results of an analysis of in vitro antiestrogenic activity indicated that only compound exhibited antiestrogenic activity; its IC value of 29.49 μM was about twice as potent as that of the reference compound, MIBP. The aromatase activity was evaluated for the synthesized target compounds and the intermediates and . A significant aromatase inhibition was observed for the intermediate and compound , with IC values of 14.5 and 17.4 μM, respectively. Compound , namely 7-methoxy-4-(2-oxo-2-(piperidin-1-yl)ethyl)-2H-chromen-2-one, could be used as an antiestrogen and/or cytotoxic agent with selective activity against tumor cells.
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http://dx.doi.org/10.3390/molecules25071553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181245PMC
March 2020

Benzoxazole derivatives as new generation of anti-breast cancer agents.

Bioorg Chem 2020 03 21;96:103593. Epub 2020 Jan 21.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, 21521 Alexandria, Egypt.

New 2-substituted benzoxazole derivatives were synthesized and screened for their in vitro anti-proliferative activities against MCF-7 and MDA-MB-231 cell lines. Compounds 4b, 4d and 11c eliciting the highest activity against MCF-7 cells were further assayed for their cytotoxic activities against A431 and HCC827 cancer cells in addition to their in vitro inhibition of wild and mutated epidermal growth factor receptor (EGFR) enzymes. Compound 11c was the most active against A431 cells and it displayed a potent inhibition of EGFR while compounds 4b and 4d elicited higher potencies than erlotinib against mutated EGFR. Compounds 4a, 6c and 8a showed the most potent cytotoxic activity against MDA-MB-231 cancer cells where compounds 4a and 6c were slightly less potent aromatase (ARO) inhibitors than letrozole. MCF-7 cells treated with compounds 4b, 4d, 11c and MDA-MB-231 cells treated with compounds 4a, 6c and 8a showed remarkable over-expression of caspase-9 protein level and elicited pre G1 apoptosis and cell cycle arrest at G2/M phase in addition to high annexin V binding affinity indicating significant apoptosis. Chemo-informatic and docking properties were also predicted. Docking results revealed that docked compounds displayed binding modes with EGFR and ARO enzymes comparable to that of the reference ligands. The benzoxazole derivatives 11c and 6c possessing amide and dithiocarbamate moieties respectively were found to be potent apoptosis-inducing anti-breast cancer agents with acceptable physicochemical properties. They exert their activity via inhibition of EGFR and ARO enzymes respectively.
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http://dx.doi.org/10.1016/j.bioorg.2020.103593DOI Listing
March 2020

Pyrazoles containing thiophene, thienopyrimidine and thienotriazolopyrimidine as COX-2 selective inhibitors: Design, synthesis, in vivo anti-inflammatory activity, docking and in silico chemo-informatic studies.

Bioorg Chem 2019 04 18;85:541-557. Epub 2019 Feb 18.

Pharmacology Department, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt; Department of Veterinary Medicine, Faculty of Agricultural and Veterinary Medicine, Qassim University, P.O. Box 1482, Buraydah, Al-Qassim, Saudi Arabia.

New thiophene and annulated thiophene pyrazole hybrids were synthesized and screened for their in vitro COX-1/COX-2 enzymatic inhibition and in vivo anti-inflammatory activities. All compounds were more COX-2 selective inhibitors than COX-1 with compound 13 exhibiting the highest COX-2 selectivity index. Compounds 3, 6a, 9 and 11 were the most promising in the acute anti-inflammatory assay while compounds 3, 5, 6a, 6c, 9, 10, 11 and 13 exerted promising anti-inflammatory activity in the sub-acute anti-inflammatory assay. Compounds 3, 6a, 6c, 9, 10 and 11 were evaluated for their ED values and were more potent than diclofenac sodium while compounds 6a, 6c and 9 were of greater potency than celecoxib with compound 6a being the most potent showing ED = 0.033 mmol/kg. These compounds were non-toxic and proved to be gastrointestinal safe compared to indomethacin, diclofenac sodium and celecoxib. Docking studies into COX-2 active site (PDB code 3LN1) revealed that compounds 3, 6a, 6c, 9, 10, 11 and 13 had binding modes and energies comparable to that of celecoxib. Compounds 3, 9, 10 and 11 complied with Lipinski's RO5 while compounds 6a and 6c showed one violation whereas compound 13 deviated by 2 violations. Compounds 6a, 6c and 13 showed 100% plasma protein binding (PPB) and showed no aqueous solubility while compounds 3, 10 and 11 demonstrated the best drug likeness model scores. Therefore, the thiophene analog 3 and the thienopyrimidine derivatives 10 and 11 are promising anti-inflammatory candidates that exert moderate selective COX-2 inhibition with acceptable physicochemical properties.
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http://dx.doi.org/10.1016/j.bioorg.2019.02.036DOI Listing
April 2019

Design and synthesis of some β-carboline derivatives as multi-target anticancer agents.

Future Med Chem 2018 12 12;10(24):2791-2814. Epub 2018 Dec 12.

Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.

Aim: Some anticancer β-carbolines exhibited dual inhibition of topo-I and KSP.

Methodology/results: Novel β-carbolines were synthesized and screened for their anticancer activity according to the NCI protocol. Five dose assays results indicated that compounds 9, 10, 12, 17 and 20 were potent and non selective anticancer agents; the sulfanyltriazole 12 was the most potent. Compounds 10, 12 and 20 showed dual topo-I and KSP inhibition with compound 12 being the most potent. Active compounds elicited Pre-G1 apoptosis and cell cycle arrest at G2/M phase of melanoma MDA-MB-435 cells. Docking results, in silico physicochemical and absorption, distribution, metabolism, excretion (ADME) properties were appropriate.

Conclusion: Compounds 10, 12 and 20 are potent apoptosis-inducing multitarget anticancer agents that act via dual inhibition of topo-I and KSP-ATPase.
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http://dx.doi.org/10.4155/fmc-2018-0226DOI Listing
December 2018

Design, synthesis, anticancer screening, docking studies and in silico ADME prediction of some β-carboline derivatives.

Future Med Chem 2018 05 22;10(10):1159-1175. Epub 2018 May 22.

Regional Center for Mycology & Biotechnology, Al-Azhar University, Cairo, Egypt.

Background: Medicinal interest has focused on β-carbolines as anticancer agents.

Methodology/results: Several β-carbolines were designed, synthesized and evaluated for their cytotoxic activity against MCF-7 and A-549 cancer cell lines using MTT assay. Compounds 13a, 13c, 13d and 20a were the most promising showing high selectivity indices. Compounds 13c and 20a showed potent inhibition of topoisomerase (topo-I) and kinesin spindle protein (KSP/Eg5 ATPase) which was confirmed by their docking results into the active site of both enzymes. In silico physicochemical calculations predicted that compounds 13a, 13d and 20a obeyed Lipinski's rule of five.

Conclusion: Compounds 13c and 20a are multitarget anticancer leads that act as potent inhibitors for both topo-I and/or KSP ATPase.
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http://dx.doi.org/10.4155/fmc-2017-0206DOI Listing
May 2018

Design, facile synthesis and anthelmintic activity of new -substituted 6-methoxybenzothiazole-2-carbamates. Part II.

Medchemcomm 2017 Jul 12;8(7):1440-1451. Epub 2017 May 12.

Department of Pathology and Parasitology, Faculty of Veterinary Medicine, Edfina , Alexandria University , Egypt.

In the framework of pursuing the design and synthesis of a new series of substituted 6-methoxybenzothiazole-2-carbamates as potential anthelmintics, and as a continuation of the expended efforts in part I, we have set out to develop novel compounds with enhanced anthelmintic activity by blocking the 6-position of benzothiazole with side chains of different polarities. Guided by the findings in part I, and reporting the paramphistomicidal activity of oxadiazoline derivatives and , we aimed to synthesize target benzothiazoles designed to comprise some planar heterocyclic ring systems, namely, 1,3,4-oxadiazoles and 1,2,4-triazoles, bearing a variety of hydrophobic and hydrophilic components. The synthesis of the desired compounds was primarily achieved by cyclization of 6-acetohydrazide, . The paramphistomicidal activity of all synthesized carbamates was evaluated. Four synthesized carbamates exhibited notable activity. Compound , methyl 6-[(5-(4-bromophenacylsulfanyl)-[1,3,4]-oxadiazol-2-yl)methoxy]benzothiazole-2-carbamate, displayed an equipotent effect to the reference drug oxyclozanide at a concentration of 80 μg mL; compounds , and showed high orders of anthelmintic effect. A structural computational study on the polar nature and hydrophilic-lipophilic properties of the synthesized carbamates was undertaken to discuss their structure-activity relationship (SAR). Besides, pharmacophore mapping was performed using eight active compounds as a training set. The generated pharmacophore model revealed five common features and was validated using fenbendazole, triclabendazole and triclabendazole sulfoxide.
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http://dx.doi.org/10.1039/c7md00140aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072514PMC
July 2017

Synthesis and biological evaluation of novel N3-substituted dihydropyrimidine derivatives as T-type calcium channel blockers and their efficacy as analgesics in mouse models of inflammatory pain.

Bioorg Med Chem 2017 03 13;25(6):1926-1938. Epub 2017 Feb 13.

Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA. Electronic address:

Low-voltage-activated calcium channels are important regulators of neurotransmission and membrane ion conductance. A plethora of intracellular events rely on their modulation. Accordingly, they are implicated in many disorders including epilepsy, Parkinson's disease, pain and other neurological diseases. Among different subfamilies, T-type calcium channels, and in particular the Ca3.2 isoform, were shown to be involved in nociceptive neurotransmission. The role of Ca3.2 in pain modulation was supported by demonstrating selective antisense oligonucleotide-mediated Ca3.2 knockdown, in vivo antinociceptive effects of T-type blockers, and pain attenuation in Ca3.2 knockout formalin-induced pain model. These Emerging investigations have provided new insights into targeting T-type calcium channels for pain management. Within this scope, various T-type calcium channel blockers have been developed such as mibefradil and ethosuximide. Although being active, most of these molecules interact with other receptors as well. This addresses the need for T-selectivity. Few selective T-type channel blockers of diverse chemical classes were developed such as ABT-639 and TTA-P2. Interestingly, R(-) efonidipine which is a dihydropyridine (DHP) showed T-channel selectivity. Systematic modification of 1,4-dihydropyridine scaffold introduced novel derivatives with 40-fold T-type selectivity over L-type calcium channels. Along these lines, substitution of the DHP core with various analogues favored T-selectivity and may serve as novel pharmacophores. Several dihydropyrimidine (DHPM) mimics were introduced by Squibb as potential candidates. As a continuation of this approach, the current study describes the synthesis of Novel N3 substituted DHPMs with structure similarities to the active DHPs. Different functional groups were introduced to the N3 position through a spacer to gain more information about activity and selectivity. Furthermore, the spacer aims at improving the metabolic stability of the molecules. Initial screening data by whole patch clamp technique showed a robust inhibition of Ca3.2 T-type channels by eleven compounds. Interestingly, four compounds of these were efficient selective T-type blockers. Based on selectivity and efficiency, two compounds were selected for in vivo evaluation in mouse models of inflammatory pain. Results showed effective attenuation of nociception and mechanical hypersensitivity.
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http://dx.doi.org/10.1016/j.bmc.2017.02.015DOI Listing
March 2017

Ethyl 5-methyl-7-phenyl-1,2,4-triazolo[4,3-a]pyrimidine-6-carboxyl-ate.

Acta Crystallogr Sect E Struct Rep Online 2014 Jun 17;70(Pt 6):o672-3. Epub 2014 May 17.

National Institute of Oceanography and Fisheries, Alexandria University, Alexandria 21556, Egypt.

In the title compound, C15H14N4O2, the triazolo-pyrimidine ring system is almost planar (r.m.s. deviation = 0.02 Å) and the phenyl ring is inclined to its mean plane by 42.45 (9)°. The carboxyl group is inclined to the triazolo-pyrimidine ring mean plane by 57.8 (3)°. In the mol-ecule, there is a short C-H⋯O contact involving the carbonyl O atom and an H atom of the adjacent methyl substituent. In the crystal, neighbouring mol-ecules are linked by C-H⋯O hydrogen bonds, forming chains propagating along [010]. There are also weak π-π inter-actions present involving the pyridine and phenyl rings of neighbouring chains [inter-centroid distance = 3.8580 (16) Å].
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http://dx.doi.org/10.1107/S1600536814010113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051068PMC
June 2014