Browsing by Author "Taher, Azza T"

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Comparative Study of the Synthetic Approaches and Biological Activities of the Bioisosteres of 1,3,4-Oxadiazoles and 1,3,4-Thiadiazoles over the Past Decade
(MDPI, 22/04/2022) El-Masry, Rana M; Kadry, Hanan H; Taher, Azza T; Abou-Seri, Sahar M
The bioisosteres of 1,3,4-oxadiazoles and 1,3,4-thiadiazoles are well-known pharma- cophores for many medicinally important drugs. Throughout the past 10 years, 1,3,4-oxa-/thiadiazole nuclei have been very attractive to researchers for drug design, synthesis, and the study of their potential activity towards a variety of diseases, including microbial and viral infections, cancer, diabetes, pain, and inflammation. This work is an up-to-date comparative study that identifies the differences between 1,3,4-thiadiazoles and 1,3,4-oxadiazoles concerning their methods of synthesis from different classes of starting compounds under various reaction conditions, as well as their biological activities and structure–activity relationship.
Evaluation of N-phenyl-2-aminothiazoles for treatment of multi-drug resistant and intracellular Staphylococcus aureus infections
(Elsevier Masson SAS, 9/15/2020) Shahin, Inas G.; Abutaleb, Nader S.; Alhashimi, Marwa; .Kassab, Asmaa E; Mohamed, Khaled O; Taher, Azza T; Seleem, Mohamed N; Mayhoub, Abdelrahman S.
European Journal of Medicinal Chemistry Volume 202, 15 September 2020, 112497 Research paper Evaluation of N-phenyl-2-aminothiazoles for treatment of multi-drug resistant and intracellular Staphylococcus aureus infections Author links open overlay panelInas G.Shahina1Nader S.Abutalebb1MarwaAlhashimibAsmaa E.KassabcKhaled O.MohamedcAzza T.TahercdMohamed N.SeleembeAbdelrahman S.Mayhoubfg a Organic Chemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts, Giza, 11787, Egypt b Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA c Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt d Department of Pharmaceutical Organic Chemistry, College of Pharmacy, October 6 University, 6-October, Giza, Egypt e Purdue Institute of Inflammation, Immunology, and Infectious Disease, West Lafayette, IN, 47907, USA f Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al- Azhar University, Cairo, 11884, Egypt g University of Science and Technology, Nanoscience Program, Zewail City of Science and Technology, October Gardens, 6th October, Giza, 12578, Egypt Received 9 December 2019, Revised 16 February 2020, Accepted 19 May 2020, Available online 25 June 2020. crossmark-logo https://doi.org/10.1016/j.ejmech.2020.112497 Get rights and content Highlights • N-Phenyl-2-aminothiazoles was defined as a potent scaffold for beating MDR-pathogens. • Aminoguanidine is an essential structural element for antimicrobial activity. • The most potent derivatives were active against linezolid and vancomycin-resistant staphylococci/enterococci. • 3e reduced the intracellular pathogen population by about 99%. • 3e displayed metabolic stability when subjected to human liver microsomes. Abstract The increasing emergence of antibiotic-resistant bacterial pathogens calls for additional urgency in the development of new antibacterial candidates. N-Phenyl-2-aminothiazoles are promising candidates that possess potent anti-MRSA activity and could potentially replenish the MRSA antibiotic pipeline. The initial screen of a series of compounds in this novel class against several bacterial strains revealed that the aminoguanidine analogues possessed promising activities and superior safety profiles. The determined MICs of these compounds were comparable to, if not better than, those of the control drugs (linezolid and vancomycin). Remarkably, compounds 3a, 3b, and 3e possessed potent activities against multidrug resistant staphylococcal isolates and several clinically important pathogens, such as vancomycin-resistant enterococci (VRE) and Streptococcus pneumoniae. In addition, the compounds were superior to vancomycin in the rapid killing of MRSA and the longer post-antibiotic effects. Furthermore, low concentrations of compounds 3a, 3b, and 3e reduced the intracellular burden of MRSA by greater than 90%. Initial in vitro PK/toxicity assessments revealed that compound 3e was highly tolerable and possessed a low metabolic clearance rate and a highly acceptable half-life.
New 5-Aryl-1,3,4-Thiadiazole-Based Anticancer Agents: Design, Synthesis, In Vitro Biological Evaluation and In Vivo Radioactive Tracing Studies
(Multidisciplinary Digital Publishing Institute (MDPI), 2022-11) El-Masry, Rana M; Essa, Basma M; Selim, Adli A; El-Emam, Soad Z; Mohamed, Khaled O; Sakr, Tamer M; Kadry, Hanan H; Taher, Azza T; Abou-Seri, Sahar M
A new series of 5-(4-chlorophenyl)-1,3,4-thiadiazole-based compounds featuring pyri- dinium (3), substituted piperazines (4a–g), benzyl piperidine (4i), and aryl aminothiazoles (5a–e) heterocycles were synthesized. Evaluation of the cytotoxicity potential of the new compounds against MCF-7 and HepG2 cancer cell lines indicated that compounds 4e and 4i displayed the highest activity toward the tested cancer cells. A selectivity study demonstrated the high selective cytotoxicity of 4e and 4i towards cancerous cells over normal mammalian Vero cells. Cell cycle analysis revealed that treatment with either compound 4e or 4i induced cell cycle arrest at the S and G2/M phases in HepG2 and MCF-7 cells, respectively. Moreover, the significant increase in the Bax/Bcl-2 ratio and caspase 9 levels in HepG2 and MCF-7 cells treated with either 4e or 4i indicated that their cytotoxic effect is attributed to the ability to induce apoptotic cell death. Finally, an in vivo radioactive tracing study of compound 4i proved its targeting ability to sarcoma cells in a tumor-bearing mice model.
Newly synthesized series of oxoindole–oxadiazole conjugates as potential anti-SARS-CoV-2 agents: in silico and in vitro studies
(Royal society of chemistry, 04/02/2022) El-Masry, Rana M; Al-Karmalawy, Ahmed A; Alnajjar, Radwan; Mahmoud, Sara H; Mostafa, Ahmed; Kadry, Hanan H; Abou-Seri, Sahar M; Taher, Azza T
In this study, a series of 1,3,4-oxadiazoles carrying the isatin moiety (IVa–g) as anti-SARS-CoV-2 agents were designed and synthesized. Molecular docking of the compounds (IVa–g) into the SARS-CoV-2 Mpro active site showed promising binding affinities. The docking results were supported using molecular dynamics simulations and MM-GBSA calculations as well. To validate the in silico predictions, all compounds were evaluated for their half-maximal cytotoxicity (CC50) and virus-inhibitory (IC50) concentrations. The CC50 concentrations were remarkably high for most of the tested compounds. However, compounds IVe and IVg showed high activity against SARS-CoV-2 at IC50 values of 13.84 μM and 4.63 μM, with selectivity indices of 4.1 and 5.9, respectively. The most potent antiviral agent IVg demonstrated an IC50 of 16.6 μM against SARS-CoV-2 Mpro, which is considered a moderate activity. However, the represented cellular antiviral activity of IVg could justify further optimization to develop this series of compounds as broad-spectrum anti-SARS-CoV-2 agents.