Publications by authors named "Mona S El-Zoghbi"

6 Publications

  • Page 1 of 1

New benzothieno[2,3-]pyridines as non-steroidal CYP17 inhibitors: design, synthesis, anticancer screening, apoptosis induction, and ADME profile studies.

J Enzyme Inhib Med Chem 2021 Dec;36(1):1839-1859

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt.

A series of [1]benzothieno[2,3-]pyridines was synthesised. Most compounds were chosen by NCI-USA to evaluate their anticancer activity. Compounds showed prominent growth inhibition against most cell lines. was selected at five dose concentration levels. It exhibited potent broad-spectrum anticancer activity with a GI of 4 nM-37 µM. Cytotoxicity of was further evaluated against prostate, renal, and breast cancer cell lines. showed double and quadruple the activity of staurosporine and abiraterone, respectively, against the PC-3 cell line with IC 2.08 µM. The possible mechanism of anti-prostate cancer was explored measuring the CYP17 enzyme activity in mice prostate cancer models compared to abiraterone. The results revealed that suppressed the CYP17 enzyme to 15.80 nM. Moreover, it was found to be equipotent to abiraterone in testosterone production. Cell cycle analysis and apoptosis were performed. Additionally, the ADME profile of compound demonstrated both good oral bioavailability and metabolic stability.
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http://dx.doi.org/10.1080/14756366.2021.1958212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330742PMC
December 2021

From triazolophthalazines to triazoloquinazolines: A bioisosterism-guided approach toward the identification of novel PCAF inhibitors with potential anticancer activity.

Bioorg Med Chem 2021 Jul 5;42:116266. Epub 2021 Jun 5.

Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11884, Cairo, Egypt; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Horus University - Egypt, International Coastal Road, 34518 New Damietta, Egypt. Electronic address:

Inhibition of PCAF bromodomain has been validated as a promising strategy for the treatment of cancer. In this study, we report the bioisosteric modification of the first reported potent PCAF bromodomain inhibitor, L-45 to its triazoloquinazoline bioisosteres. Accordingly, three new series of triazoloquinazoline derivatives were designed, synthesized, and assessed for their anticancer activity against a panel of four human cancer cells. Three derivatives demonstrated comparable cytotoxic activity with the reference drug doxorubicin. Among them, compound 22 showed the most potent activity with IC values of 15.07, 9.86, 5.75, and 10.79 µM against Hep-G2, MCF-7, PC3, and HCT-116 respectively. Also, compound 24 exhibited remarkable cytotoxicity effects against the selected cancer cell lines with IC values of 20.49, 12.56, 17.18, and 11.50 µM. Compounds 22 and 25 were the most potent PCAF inhibitors (IC, 2.88 and 3.19 μM, respectively) compared with bromosporine (IC, 2.10 μM). Follow up apoptosis induction and cell cycle analysis studies revealed that the bioisostere 22 could induce apoptotic cell death and arrest the cell cycle of PC3 at the G2/M phase. The in silico molecular docking studies were additionally performed to rationalize the PCAF inhibitory effects of new triazoloquinazoline bioisosteres.
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http://dx.doi.org/10.1016/j.bmc.2021.116266DOI Listing
July 2021

Synthesis, molecular modeling and biological evaluation of new benzo[4,5]thieno[3,2-b]pyran derivatives as topoisomerase I-DNA binary complex poisons.

Bioorg Chem 2021 07 15;112:104915. Epub 2021 Apr 15.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Menoufia University, Shibin El kom, Gamal Abd El-Nasir Street, Menoufia, Egypt. Electronic address:

A series of new benzo[b]thiophenes 2a-f and benzo[4,5]thieno[3,2-b]pyran derivatives 3a-f and 4a-f were synthesized and their structures were confirmed by elemental analyses and spectral data. All synthesized compounds were evaluated by the National Cancer Institute (NCI, USA) against 60 human tumor cell lines. Compounds 3a-f and 4a-f showed potent cytotoxic effects in one dose assay with mean growth inhibition ranging from 62% to 80%. Six compounds 3a, 3d, 3e, 3f, 4d and 4e were selected by NCI, USA for five dose evaluation against 60 human tumor cell lines. Compounds 3a, 3d, 3e and 3f exhibited very potent and broad spectrum cytotoxicity against almost all cancer cell lines with mean concentration that yield 50% growth inhibition (MG-MID GI) of 0.1-0.58 µM and mean concentration that produce 100% growth inhibition (MG-MID TGI) of 6.03-10.00 µM. Compounds 4d and 4e exhibited very potent and selective cytotoxic activity against MDA-MB-435 subpanel (melanoma cancer) with GI of 0.45 µM and 0.59 µM, respectively. The mechanism of antiproliferative activity was determined for the most active compounds 3a, 3d, 3e, 3f, 4d, and 4evia measuring their half maximal inhibitory concentration (IC) against topoisomerase I enzyme at different concentrations. Compounds 3a and 3e exhibited excellent activity compared with reference drugs with IC of 0.295 µM and 0.219 µM, respectively. Plasmid DNA nicking assay verified that these compounds are topoisomerase I poisons not suppressors. The active compound 3e induced a significant disruption in the cell cycle profile parallel to its effect on apoptosis induction.
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http://dx.doi.org/10.1016/j.bioorg.2021.104915DOI Listing
July 2021

In vivo- and in silico-driven identification of novel synthetic quinoxalines as anticonvulsants and AMPA inhibitors.

Arch Pharm (Weinheim) 2021 May 9;354(5):e2000449. Epub 2021 Feb 9.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Menoufia University, Shebin El-Koum, Egypt.

The lack of effective therapies for epileptic patients and the potentially harmful consequences of untreated seizure incidents have made epileptic disorders in humans a major health concern. Therefore, new and more potent anticonvulsant drugs are continually sought after, to combat epilepsy. On the basis of the pharmacophoric structural specifications of effective α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists with an efficient anticonvulsant activity, the present work reports the design and synthesis of two novel sets of quinoxaline derivatives. The anticonvulsant activity of the synthesized compounds was evaluated in vivo according to the pentylenetetrazol-induced seizure protocol, and the results were compared with those of perampanel as a reference drug. Among the synthesized compounds, 24, 28, 32, and 33 showed promising activities with ED values of 37.50, 23.02, 29.16, and 23.86 mg/kg, respectively. Docking studies of these compounds suggested that AMPA binding could be the mechanism of action of these derivatives. Overall, the pharmacophore-based structural optimization, in vivo and in silico docking, and druglikeness studies indicated that the designed compounds could serve as promising candidates for the development of effective anticonvulsant agents with good pharmacokinetic profiles.
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http://dx.doi.org/10.1002/ardp.202000449DOI Listing
May 2021

Comprehensive review for anticancer hybridized multitargeting HDAC inhibitors.

Eur J Med Chem 2021 Jan 8;209:112904. Epub 2020 Oct 8.

Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, New Minia, Minia, Egypt. Electronic address:

Despite the encouraging clinical progress of chemotherapeutic agents in cancer treatment, innovation and development of new effective anticancer candidates still represents a challenging endeavor. With 15 million death every year in 2030 according to the estimates, cancer has increased rising of an alarm as a real crisis for public health and health systems worldwide. Therefore, scientist began to introduce innovative solutions to control the cancer global health problem. One of the promising strategies in this issue is the multitarget or smart hybrids having two or more pharmacophores targeting cancer. These rationalized hybrid molecules have gained great interests in cancer treatment as they are capable to simultaneously inhibit more than cancer pathway or target without drug-drug interactions and with less side effects. A prime important example of these hybrids, the HDAC hybrid inhibitors or referred as multitargeting HDAC inhibitors. The ability of HDAC inhibitors to synergistically improve the efficacy of other anti-cancer drugs and moreover, the ease of HDAC inhibitors cap group modification prompt many medicinal chemists to innovate and develop new generation of HDAC hybrid inhibitors. Notably, and during this short period, there are four HDAC inhibitor hybrids have entered different phases of clinical trials for treatment of different types of blood and solid tumors, namely; CUDC-101, CUDC-907, Tinostamustine, and Domatinostat. This review shed light on the most recent hybrids of HDACIs with one or more other cancer target pharmacophore. The designed multitarget hybrids include topoisomerase inhibitors, kinase inhibitors, nitric oxide releasers, antiandrogens, FLT3 and JAC-2 inhibitors, PDE5-inhibitors, NAMPT-inhibitors, Protease inhibitors, BRD4-inhibitors and other targets. This review may help researchers in development and discovery of new horizons in cancer treatment.
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http://dx.doi.org/10.1016/j.ejmech.2020.112904DOI Listing
January 2021

Synthesis of certain benzothieno[3,2-d]pyrimidine derivatives as a selective SIRT2 inhibitors.

Eur J Med Chem 2020 Feb 30;187:111926. Epub 2019 Nov 30.

Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Menoufia University, Menoufia, Gamal Abd El-Nasir Street, Egypt. Electronic address:

A series of new benzothieno[3,2-d]pyrimidine derivatives were designed and synthesized. The National Cancer Institute (NCI, USA) evaluated all synthesized compounds against 60 human tumor cell lines. Most of the compounds showed good cytotoxicity against MCF-7 breast cancer cell line and UO-31 renal cancer cell line (growth inhibitory range: 17.88%-68.65%). IC of twelve most active compounds was determined against MCF-7 and UO-31 cell lines. Compounds 7, 10, 13, 16 and 17 proved a prominent anticancer activity against tested cell lines (IC range 0.23-26.25 μg/mL). IC against SIRT2 enzyme was evaluated for the most active compounds to explore the mechanism of antiproliferative activity. The best activity was displayed by compound 7 (IC = 2.10 μg/mL), which is 6.6 more potent than cambinol as a reference. Moreover, compound 7 displayed high selectivity against SIRT1 and SIRT2 over SIRT3 in the selectivity studies and displayed twice activity of cambinol in hyperacetylation of α-tubulin protein with IC = 32.05 μg/mL. Molecular docking study of the synthesized compounds into SIRT2 active site was performed to rationalize the remarkable SIRT2 inhibitory activity.
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http://dx.doi.org/10.1016/j.ejmech.2019.111926DOI Listing
February 2020
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