Novel fluorescence approach for trace quantification of levonorgestrel in breast milk based on click reaction with benzonitrofurazan azide (NBD-AZ) Heba A Aref, Ismail Salama, Shaimaa Mohamed Aboukhatwa, Mohamed A Helal, Safaa M Kishk, et al. Methods and Applications in Fluorescence, 2024 Although the great importance of oral contraceptive agents in birth control, their existence in breast milk became a cause for concern, since infant exposure to these hormones is associated with many health problems. Consequentially, developing a sensitive bioanalytical method for monitoring their concentrations in breast milk is an urgent demand to examine the safety or the risk of these compounds on infants. Levonorgestrel is one of the most common contraceptive hormones under concern. Despite the high sensitivity of the fluorometric methods, detection of Levonorgestrel by them is confined because its structure does not exhibit any fluorescence. For the first time, we proposed a promising click fluorescent probe, 4-azido-7-nitrobenzoxadiazole to react with the alkyne group of Levonorgestrel, to give a highly fluorescent triazole derivative that exhibited strong signal at wavelength of 544 nm after excitation at 470 nm. Reaction parameters impacting the fluorescence were cautiously studied and optimized. The suggested approach has been successfully applied in Levonorgestrel estimation in breast milk samples with linearity of (0.4–80 ng.ml−1) and low detection limit of 0.12 ng.ml−1 without interferences from any biological components and with mean % recovery of 97.84 ± 2.73. Accuracy, sensitivity, selectivity, simplicity, and low-cost makes this approach a convincing, promising, and appealing alternative over reported analytical methods for Levonorgestrel bioanalysis in different matrices.
Prospective Antiviral Effect of Ulva lactuca Aqueous Extract against COVID-19 Infection Reem Binsuwaidan, Thanaa A. El-Masry, Mostafa El-Sheekh, Mohamed G. Seadawy, Mofida E. M. Makhlof, et al. Marine Drugs, 2024 Marine algal extracts exhibit a potent inhibitory effect against several enveloped and non-enveloped viruses. The infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has several adverse effects, including an increased mortality rate. The anti-COVID-19 agents are still limited; this issue requires exploring novel, effective anti-SARS-CoV-2 therapeutic approaches. This study investigated the antiviral activity of an aqueous extract of Ulva lactuca, which was collected from the Gulf of Suez, Egypt. The aqueous extract of Ulva lactuca was characterized by high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Energy Dispersive X-ray (EDX) analyses. According to the HPLC analysis, the extract comprises several sugars, mostly rhamnose (32.88%). The FTIR spectra showed numerous bands related to the functional groups. EDX analysis confirmed the presence of different elements, such as oxygen (O), carbon (C), sulfur (S), magnesium (Mg), potassium (K), calcium (Ca), and sodium (Na), with different concentrations. The aqueous extract of U. lactuca (0.0312 mg/mL) exhibited potent anti-SARS-CoV-2 activity via virucidal activity, inhibition of viral replication, and interference with viral adsorption (% inhibitions of 64%, 33.3%, and 31.1%, respectively). Consequently, ulvan could be a promising compound for preclinical study in the drug development process to combat SARS-CoV-2.
4-Azido-7-nitrobenzoxadiazole as innovative clickable fluorescence probe for trace and selective quantification of ethinylestradiol in human plasma Heba A. Aref, Ismail Salama, Shaimaa Mohamed Aboukhatwa, Mohamed A. Helal, Safaa M. kishk, et al. Luminescence, 2023 Quantification of ethinylestradiol (EE) in biological matrices is challenging as it is a very potent drug with a very low Cmax (75 pg.ml−1). Despite the high sensitivity of fluorometric methods, the detection of EE was confined because its structure exhibited very limited fluorescence. Therefore, it must be derivatized first using a fluorogenic agent to produce a more potent fluorescence derivative to achieve the desired ultrasensitive bioanalysis. Here, for the first time, we proposed a promising click fluorescent probe, 4‐azido‐7‐nitrobenzoxadiazole (NBD‐AZ) to react with the alkyne group of EE, with the help of copper sulphate and l‐ascorbic acid to give a highly fluorescent and stable 1,2,3‐triazole derivative. Density functional theory calculation revealed how the triazole formation affects the quantum yield and fluorescence of click reaction product when compared with NBD‐AZ. The resulting triazole exhibited a strong signal at a wavelength of 540 nm after excitation at 470 nm. Reaction parameters impacting the intensity of fluorescence were cautiously studied and optimized. The suggested approach has shown outstanding performance, high linearity (25–300 pg.ml−1) and a low detection limit of 7.5 pg.ml−1. The enhanced sensitivity and selectivity were exploited for analyzing EE in plasma using liquid–liquid extraction for samples cleaning up without interference from any biological components and with a mean % recovery of 100.13 ± 0.39. Accuracy, sensitivity, selectivity, simplicity, and cost–effectiveness make this approach a convincing, promising, and appealing alternative to the reported analytical methods for EE bioanalysis in different matrices.
Terminators or Guardians? Design, Synthesis, and Cytotoxicity Profiling of Chalcone-Sulfonamide Hybrids Shaimaa M. Aboukhatwa, Peter A. Sidhom, Andrea Angeli, Claudiu T. Supuran, Haytham O. Tawfik ACS Omega, 2023 With a “less is more” philosophy, a series of 15 chalcone-sulfonamide hybrids were designed anticipating synergistic anticancer activity. The aromatic sulfonamide moiety was included as a known direct inhibitor of carbonic anhydrase IX activity through its zinc chelating property. The chalcone moiety was incorporated as an electrophilic stressor to indirectly inhibit carbonic anhydrase IX cellular activity. Screening by the Developmental Therapeutics Program of the National Cancer Institute, NCI-60, revealed that 12 derivatives were potent inhibitors of cancer cell growth in multiple cell lines and were promoted to the five-dose screen. The cancer cell growth inhibition profile indicated sub- to two-digit micromolar potency (GI50 down to 0.3 μM and LC50 as low as 4 μM) against colorectal carcinoma cells, in particular. Unexpectedly, most compounds demonstrated low to moderate potency as direct inhibitors of carbonic anhydrase catalytic activity in vitro, with 4d being the most potent, having an average Ki value of 4 μM. Compound 4j showed ca. six-fold selectivity to carbonic anhydrase IX over the other tested isoforms in vitro. Cytotoxicity of both 4d and 4j in live HCT116, U251, and LOX IMVI cells under hypoxic conditions confirmed their targeting of carbonic anhydrase activity. Elevation of oxidative cellular stress was stipulated from the increase in Nrf2 and ROS levels in 4j-treated colorectal carcinoma, HCT116, cells compared to the control. Compound 4j arrested the cell cycle of HCT116 cells at the G1/S phase. In addition, both 4d and 4j showed up to 50-fold cancer cell selectivity compared to the non-cancerous HEK293T cells. Accordingly, this study presents 4d and 4j being new, synthetically accessible, simplistically designed derivatives as potential candidates to be further developed as anticancer therapeutics.
Isonicotinic acid N-oxide, from isoniazid biotransformation by Aspergillus niger, as an InhA inhibitor antituberculous agent against multiple and extensively resistant strains supported by in silico docking and ADME prediction Amany E. Ragab, Ebtisam T. Badawy, Shaimaa M. Aboukhatwa, Marwa M. Abdel-Aziz, Amal Kabbash, et al. Natural Product Research, 2023 Biotransformation of isoniazid produced isonicotinic acid (1), isonicotinic acid N-oxide (2), and isonicotinamide (3) which were isolated by column chromatography using silica gel and Sephadex LH 20 and elucidated using various spectroscopies. This is the first report for isolation of 2 . Antituberculosis activity was evaluated against Mycobacterium tuberculosis strains: drug sensitive (DS), multiple drug resistant (MDR) and extensively drug resistant (XDR). 1-3 and isoniazid showed MICs of 63.49, 0.22, 15.98 and 0.88 µM, respectively, against the DS strain. For the MDR strain, 2 and 3 exhibited MICs of 28.06 and > 1000 µM, respectively, while 1 was inactive. Moreover, 2 had an MIC of 56.19 µM against XDR strain, while 1 and 3 were inactive. Docking simulation using enoyl ACP reductase (InhA) revealed favorable protein-ligand interactions. In silico study of pharmacokinetics and hepatotoxicity predicted 1-3 to have good oral bioavailability and 2 to have a lower hepatoxicity probability than isoniazid. Graphical Abstract
Bioactive galloylquinic acids from Copaifera lucens as dual inhibitors of SARS-CoV-2 Spike and RdRp proteins RM El-Morsi, LA Al-Madboly, JK Bastos, SM Aboukhatwa, SA Nasr, ... Scientific Reports 16 (1), 4521 , 2026 2026.0
Synergy trap for guardian angels of DNA: Unraveling the anticancer potential of phthalazinone-thiosemicarbazone hybrids through dual PARP-1 and TOPO-I inhibition EM Elkafoury, MH El-Hamamsy, EA El-Bastawissy, K Afarinkia, ... Bioorganic Chemistry 153, 107924 , 2024 2024.0 Citations: 2
Characterization of GQA as a novel β-lactamase inhibitor of CTX-M-15 and KPC-2 enzymes LA Al-Madboly, MAA El-Salam, JK Bastos, S Aboukhatwa, RM El-Morsi Microbial Cell Factories 23 (1), 221 , 2024 2024.0 Citations: 3
Design and synthesis of quinazolin-4-one derivatives as potential anticancer agents and investigation of their interaction with RecQ helicases HS Haggag, SM Aboukhatwa, MS Nafie, A Paul, N Sharafeldin, AW Oliver, ... Bioorganic chemistry 144, 107086 , 2024 2024.0 Citations: 11
Novel fluorescence approach for trace quantification of levonorgestrel in breast milk based on click reaction with benzonitrofurazan azide (NBD-AZ) HA Aref, I Salama, SM Aboukhatwa, MA Helal, SM Kishk, MS Elgawish Methods and Applications in Fluorescence 12 (1), 015009 , 2024 2024.0
Prospective Antiviral Effect of Ulva lactuca Aqueous Extract against COVID-19 Infection R Binsuwaidan, TA El-Masry, M El-Sheekh, MG Seadawy, MEM Makhlof, ... Marine Drugs 22 (1), 30 , 2023 2023.0 Citations: 24
4‐Azido‐7‐nitrobenzoxadiazole as innovative clickable fluorescence probe for trace and selective quantification of ethinylestradiol in human plasma HA Aref, I Salama, SM Aboukhatwa, MA Helal, SM Kishk, MS Elgawish Luminescence 38 (11), 1848-1856 , 2023 2023.0 Citations: 3
Isonicotinic acid N -oxide, from isoniazid biotransformation by Aspergillus niger , as an InhA inhibitor antituberculous agent against multiple and extensively resistant strains … AE Ragab, ET Badawy, SM Aboukhatwa, MM Abdel-Aziz, A Kabbash, ... Natural Product Research 37 (10), 1687-1692 , 2023 2023.0 Citations: 7
Terminators or guardians? Design, synthesis, and cytotoxicity profiling of chalcone-sulfonamide hybrids SM Aboukhatwa, PA Sidhom, A Angeli, CT Supuran, HO Tawfik ACS omega 8 (8), 7666-7683 , 2023 2023.0 Citations: 27
Click chemistry as a promising protocol for fluorogenic reactions HA Aref, MA Helal, S Kishk, S Aboukhatwa, I Salama Records of Pharmaceutical and Biomedical Sciences 7 (1), 154-166 , 2023 2023.0 Citations: 1
Nicotinonitrile-derived apoptotic inducers: Design, synthesis, X-ray crystal structure and Pim kinase inhibition SM Aboukhatwa, AO Ibrahim, H Aoyama, AS Al-Behery, MA Shaldam, ... Bioorganic Chemistry 129, 106126 , 2022 2022.0 Citations: 23
In vitro characterization of inhibitors for lung A549 and leukemia K562 cell lines from fungal transformation of arecoline supported by in silico docking to M3-mAChR and ADME … AE Ragab, ET Badawy, SM Aboukhatwa, A Kabbash, KA Abo El-Seoud Pharmaceuticals 15 (10), 1171 , 2022 2022.0 Citations: 12
Structurally Diverse Histone Deacetylase Photoreactive Probes: Design, Synthesis, and Photolabeling Studies in Live Cells and Tissue SM Aboukhatwa, TW Hanigan, TY Taha, J Neerasa, R Ranjan, ... ChemMedChem 14 (11), 1096-1107 , 2019 2019.0 Citations: 6
Unexpected selectivity of histone deacetylase inhibitors in live MDA-MD-231 triple-negative breast cancer cells SM Aboukhatwa, TW Hanigan, J Neerasa, TY Taha, ND Brown, ... Cancer Research 78 (13_Supplement), 5801-5801 , 2018 2018.0
Divergent JNK phosphorylation of HDAC3 in triple-negative breast cancer cells determines HDAC inhibitor binding and selectivity TW Hanigan, SM Aboukhatwa, TY Taha, J Frasor, PA Petukhov Cell chemical biology 24 (11), 1356-1367. e8 , 2017 2017.0 Citations: 42
Scaffold dependent histone deacetylase (HDAC) inhibitor induced re-equilibration of the subcellular localization and post-translational modification state of class I HDACs TW Hanigan, TY Taha, SM Aboukhatwa, J Frasor, PA Petukhov PloS one 12 (10), e0186620 , 2017 2017.0 Citations: 5
Design, synthesis, and biological evaluation of tetrahydroisoquinoline-based histone deacetylase 8 selective inhibitors TY Taha, SM Aboukhatwa, RC Knopp, N Ikegaki, H Abdelkarim, ... ACS Medicinal Chemistry Letters 8 (8), 824-829 , 2017 2017.0 Citations: 45
Design Studies of Drugs for the Management of HBV Infection S Aboukhatwa Faculty of Pharmacy, Tanta University , 2012 2012.0
Novel Clickable Fluorescence Probe: Benzonitrofurazan-Azide for Trace and Selective Quantification of Ethinylestradiol in Spiked Human Plasma I Salama, S Aboukhatwa, MA Helal, M Elgawish
MOST CITED SCHOLAR PUBLICATIONS
Design, synthesis, and biological evaluation of tetrahydroisoquinoline-based histone deacetylase 8 selective inhibitors TY Taha, SM Aboukhatwa, RC Knopp, N Ikegaki, H Abdelkarim, ... ACS Medicinal Chemistry Letters 8 (8), 824-829 , 2017 2017.0 Citations: 45
Divergent JNK phosphorylation of HDAC3 in triple-negative breast cancer cells determines HDAC inhibitor binding and selectivity TW Hanigan, SM Aboukhatwa, TY Taha, J Frasor, PA Petukhov Cell chemical biology 24 (11), 1356-1367. e8 , 2017 2017.0 Citations: 42
Terminators or guardians? Design, synthesis, and cytotoxicity profiling of chalcone-sulfonamide hybrids SM Aboukhatwa, PA Sidhom, A Angeli, CT Supuran, HO Tawfik ACS omega 8 (8), 7666-7683 , 2023 2023.0 Citations: 27
Prospective Antiviral Effect of Ulva lactuca Aqueous Extract against COVID-19 Infection R Binsuwaidan, TA El-Masry, M El-Sheekh, MG Seadawy, MEM Makhlof, ... Marine Drugs 22 (1), 30 , 2023 2023.0 Citations: 24
Nicotinonitrile-derived apoptotic inducers: Design, synthesis, X-ray crystal structure and Pim kinase inhibition SM Aboukhatwa, AO Ibrahim, H Aoyama, AS Al-Behery, MA Shaldam, ... Bioorganic Chemistry 129, 106126 , 2022 2022.0 Citations: 23
In vitro characterization of inhibitors for lung A549 and leukemia K562 cell lines from fungal transformation of arecoline supported by in silico docking to M3-mAChR and ADME … AE Ragab, ET Badawy, SM Aboukhatwa, A Kabbash, KA Abo El-Seoud Pharmaceuticals 15 (10), 1171 , 2022 2022.0 Citations: 12
Design and synthesis of quinazolin-4-one derivatives as potential anticancer agents and investigation of their interaction with RecQ helicases HS Haggag, SM Aboukhatwa, MS Nafie, A Paul, N Sharafeldin, AW Oliver, ... Bioorganic chemistry 144, 107086 , 2024 2024.0 Citations: 11
Isonicotinic acid N -oxide, from isoniazid biotransformation by Aspergillus niger , as an InhA inhibitor antituberculous agent against multiple and extensively resistant strains … AE Ragab, ET Badawy, SM Aboukhatwa, MM Abdel-Aziz, A Kabbash, ... Natural Product Research 37 (10), 1687-1692 , 2023 2023.0 Citations: 7
Structurally Diverse Histone Deacetylase Photoreactive Probes: Design, Synthesis, and Photolabeling Studies in Live Cells and Tissue SM Aboukhatwa, TW Hanigan, TY Taha, J Neerasa, R Ranjan, ... ChemMedChem 14 (11), 1096-1107 , 2019 2019.0 Citations: 6
Scaffold dependent histone deacetylase (HDAC) inhibitor induced re-equilibration of the subcellular localization and post-translational modification state of class I HDACs TW Hanigan, TY Taha, SM Aboukhatwa, J Frasor, PA Petukhov PloS one 12 (10), e0186620 , 2017 2017.0 Citations: 5
Characterization of GQA as a novel β-lactamase inhibitor of CTX-M-15 and KPC-2 enzymes LA Al-Madboly, MAA El-Salam, JK Bastos, S Aboukhatwa, RM El-Morsi Microbial Cell Factories 23 (1), 221 , 2024 2024.0 Citations: 3
4‐Azido‐7‐nitrobenzoxadiazole as innovative clickable fluorescence probe for trace and selective quantification of ethinylestradiol in human plasma HA Aref, I Salama, SM Aboukhatwa, MA Helal, SM Kishk, MS Elgawish Luminescence 38 (11), 1848-1856 , 2023 2023.0 Citations: 3
Synergy trap for guardian angels of DNA: Unraveling the anticancer potential of phthalazinone-thiosemicarbazone hybrids through dual PARP-1 and TOPO-I inhibition EM Elkafoury, MH El-Hamamsy, EA El-Bastawissy, K Afarinkia, ... Bioorganic Chemistry 153, 107924 , 2024 2024.0 Citations: 2
Click chemistry as a promising protocol for fluorogenic reactions HA Aref, MA Helal, S Kishk, S Aboukhatwa, I Salama Records of Pharmaceutical and Biomedical Sciences 7 (1), 154-166 , 2023 2023.0 Citations: 1
Bioactive galloylquinic acids from Copaifera lucens as dual inhibitors of SARS-CoV-2 Spike and RdRp proteins RM El-Morsi, LA Al-Madboly, JK Bastos, SM Aboukhatwa, SA Nasr, ... Scientific Reports 16 (1), 4521 , 2026 2026.0
Novel fluorescence approach for trace quantification of levonorgestrel in breast milk based on click reaction with benzonitrofurazan azide (NBD-AZ) HA Aref, I Salama, SM Aboukhatwa, MA Helal, SM Kishk, MS Elgawish Methods and Applications in Fluorescence 12 (1), 015009 , 2024 2024.0
Unexpected selectivity of histone deacetylase inhibitors in live MDA-MD-231 triple-negative breast cancer cells SM Aboukhatwa, TW Hanigan, J Neerasa, TY Taha, ND Brown, ... Cancer Research 78 (13_Supplement), 5801-5801 , 2018 2018.0
Design Studies of Drugs for the Management of HBV Infection S Aboukhatwa Faculty of Pharmacy, Tanta University , 2012 2012.0
Novel Clickable Fluorescence Probe: Benzonitrofurazan-Azide for Trace and Selective Quantification of Ethinylestradiol in Spiked Human Plasma I Salama, S Aboukhatwa, MA Helal, M Elgawish
