Publications by authors named "Fawzia Faleh Al-Blewi"

6 Publications

  • Page 1 of 1

Design, Synthesis, Molecular Modeling, Anticancer Studies, and Density Functional Theory Calculations of 4-(1,2,4-Triazol-3-ylsulfanylmethyl)-1,2,3-triazole Derivatives.

ACS Omega 2021 Jan 31;6(1):301-316. Epub 2020 Dec 31.

Chemistry Department, College of Sciences, Yanbu, Taibah University, Yanbu 30799, Saudi Arabia.

New conjugates of substituted 1,2,3-triazoles linked to 1,2,4-triazoles were synthesized starting from the appropriate S-propargylated 1,2,4-triazoles and . Ligation of 1,2,4-triazoles to the 1,2,3-triazole core was performed through Cu(I)-catalyzed cycloaddition of 1,2,4-triazole-based alkyne side chain and/or with several un/functionalized alkyl- and/or aryl-substituted azides to afford the desired 1,4-disubstituted 1,2,3-triazoles , using both classical and microwave methods. After their spectroscopic characterization (infrared, H, C nuclear magnetic resonance, and elemental analyses), an anticancer screening was carried out against some cancer cell lines including human colon carcinoma (Caco-2 and HCT116), human cervical carcinoma (HeLa), and human breast adenocarcinoma (MCF-7). The outcomes of this exploration revealed that compounds , , and had a significant anticancer activity against MCF-7 and Caco-2 cancer cell lines with IC values of 0.31 and 4.98 μM, respectively, in relation to the standard reference drug, doxorubicin. Enzyme-docking examination was executed onto cyclin-dependent kinase 2; a promising aim for cancer medication. Synthesized compounds acquiring highest potency showcased superior interactions with the active site residue of the target protein and exhibited minimum binding energy. Finally, the density functional theory (DFT) calculations were carried out to confirm the outcomes of the molecular docking and the experimental findings. The chemical reactivity descriptors such as softness (δ), global hardness (η), electronegativity (χ), and electrophilicity were calculated from the levels of the predicted frontier molecular orbitals and their energy gap. The DFT results and the molecular docking calculation results explained the activity of the most expectedly active compounds , , and .
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http://dx.doi.org/10.1021/acsomega.0c04595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807778PMC
January 2021

Synthesis, Characterization, DNA Binding, Anticancer, and Molecular Docking Studies of Novel Imidazolium-Based Ionic Liquids with Fluorinated Phenylacetamide Tethers.

ACS Omega 2020 Mar 9;5(10):4807-4815. Epub 2020 Mar 9.

Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia.

Newer imidazolium ionic liquid (IL) halides appending variety of fluorinated phenylacetamide side chains were designed and synthesized through quaternization of 1-methyl and/or 1,2-dimethylimidazole with appropriate 2-chloro--(fluorinatedphenyl)acetamides. The resulting ILs were converted to their respective ionic liquid analogues carrying fluorinated counteranions (PF , BF , and/or CFCOO) . All newly synthesized ILs were fully characterized using several spectroscopic experiments such as H, C, B, F, P NMR, and mass analysis. The synthesized ionic liquids were investigated for their DNA binding and anticancer activities. The obtained DNA binding constants ranged from 1.444 × 10 to 3.518 × 10, indicating a reasonably good binding affinity. The percentage of anticancer activities ranged from 48 to 59 with H-1229 cell line, showing quite good anticancer potential. The modeling studies indicated the interactions of the reported molecules with DNA hydrogen bonds. These were in agreement with those of DNA binding and anticancer results. Briefly, the designed ionic liquids may be used as good anticancer candidates for treating human cancer.
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http://dx.doi.org/10.1021/acsomega.9b03468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081306PMC
March 2020

Introducing of acyclonucleoside analogues tethered 1,2,4-triazole as anticancer agents with dual epidermal growth factor receptor kinase and microtubule inhibitors.

Bioorg Chem 2020 01 23;94:103446. Epub 2019 Nov 23.

Department of Chemistry, Faculty of Sciences, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia; Laboratoire de Chimie & Electrochimie des Complexes Métalliques (LCECM) USTO-MB, Department of Chemistry, Faculty of Sciences, University of Sciences and Technology Mohamed Boudiaf, B.p. 1505 El M nouar, Oran 31000, Algeria.

This study reports an efficient and convenient regioselective synthesis of a novel series of S- and S,N-bis(acyclonucleoside) analogues carrying 5-(2-chlorophenyl)-2,4-dihydro-1,2,4-triazole-3-thione. A facile and straightforward synthesis of thiazolotriazole and triazolothiazines has also been reported. Structures of all newly synthesized compounds were well characterized by infrared IR, H and C nuclear magnetic resonance (NMR) and mass (MS) spectra analyses. Cytotoxic screening was performed according to (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium (MTT) assay method using staurosporine as a reference drug against three different types: human liver cancer cell line (Hep G2), Michigan cancer foundation-7 (MCF-7) and human colorectal carcinoma cell line (HCT116). These data showed considerable anticancer activity for these newly synthesized compounds. Biological data for most of the S-acyclonucleoside analogues and S,N-bis(acyclonucleoside) analogues showed excellent activity with micromolar (µM) half maximal inhibitory concentration (IC) values against tumor cells. EGFR assay and tubulin inhibition assay analysis were performed for the most active compounds to get more details about their mechanism of action. In order to assess and explain their binding affinities, molecular docking simulation was studied against EGFR and tubulin binding sites. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated. Extensive structure activity relationship (SAR) analyses were also carried out.
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http://dx.doi.org/10.1016/j.bioorg.2019.103446DOI Listing
January 2020

Novel amphiphilic pyridinium ionic liquids-supported Schiff bases: ultrasound assisted synthesis, molecular docking and anticancer evaluation.

Chem Cent J 2018 Nov 22;12(1):118. Epub 2018 Nov 22.

Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah, Medina, 30002, Saudi Arabia.

Background: Pyridinium Schiff bases and ionic liquids have attracted increasing interest in medicinal chemistry.

Results: A library of 32 cationic fluorinated pyridinium hydrazone-based amphiphiles tethering fluorinated counteranions was synthesized by alkylation of 4-fluoropyridine hydrazone with various long alkyl iodide exploiting lead quaternization and metathesis strategies. All compounds were assessed for their anticancer inhibition activity towards different cancer cell lines and the results revealed that increasing the length of the hydrophobic chain of the synthesized analogues appears to significantly enhance their anticancer activities. Substantial increase in caspase-3 activity was demonstrated upon treatment with the most potent compounds, namely 8, 28, 29 and 32 suggesting an apoptotic cellular death pathway.

Conclusions: Quantum-polarized ligand docking studies against phosphoinositide 3-kinase α displayed that compounds 2-6 bind to the kinase site and form H-bond with S774, K802, H917 and D933.
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http://dx.doi.org/10.1186/s13065-018-0489-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768046PMC
November 2018

Design, synthesis, ADME prediction and pharmacological evaluation of novel benzimidazole-1,2,3-triazole-sulfonamide hybrids as antimicrobial and antiproliferative agents.

Chem Cent J 2018 Nov 1;12(1):110. Epub 2018 Nov 1.

Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, 21500, Egypt.

Background: Nitrogen heterocyclic rings and sulfonamides have attracted attention of several researchers.

Results: A series of regioselective imidazole-based mono- and bis-1,4-disubstituted-1,2,3-triazole-sulfonamide conjugates 4a-f and 6a-f were designed and synthesized. The first step in the synthesis was a regioselective propargylation in the presence of the appropriate basic catalyst (EtN and/or KCO) to afford the corresponding mono-2 and bis-propargylated imidazoles 5. Second, the ligation of the terminal C≡C bond of mono-2 and/or bis alkynes 5 to the azide building blocks of sulfa drugs 3a-f using optimized conditions for a Huisgen copper (I)-catalysed 1,3-dipolar cycloaddition reaction yielded targeted 1,2,3-triazole hybrids 4a-f and 6a-f. The newly synthesized compounds were screened for their in vitro antimicrobial and antiproliferative activities. Among the synthesized compounds, compound 6a emerged as the most potent antimicrobial agent with MIC values ranging between 32 and 64 µg/mL. All synthesized molecules were evaluated against three aggressive human cancer cell lines, PC-3, HepG2, and HEK293, and revealed sufficient antiproliferative activities with IC values in the micromolar range (55-106 μM). Furthermore, we conducted a receptor-based electrostatic analysis of their electronic, steric and hydrophobic properties, and the results were in good agreement with the experimental results. In silico  ADMET prediction studies also supported the experimental biological results and indicated that all compounds are nonmutagenic and noncarcinogenic.

Conclusion: In summary, we have successfully synthesized novel targeted benzimidazole-1,2,3-triazole-sulfonamide hybrids through 1,3-dipolar cycloaddition reactions between the mono- or bis-alkynes based on imidazole and the appropriate sulfonamide azide under the optimized Cu(I) click conditions. The structures of newly synthesized sulfonamide hybrids were confirmed by means of spectroscopic analysis. All newly synthesized compounds were evaluated for their antimicrobial and antiproliferative activities. Our results showed that the benzimidazole-1,2,3-triazole-sulfonamide hybrids inhibited microbial and fungal strains within MIC values from 32 to 64 μg/mL. The antiproliferative evaluation of the synthesized compounds showed sufficient antiproliferative activities with IC values in the micromolar range (55-106 μM). In conclusion, compound 6a has remarkable antimicrobial activity. Pharmacophore elucidation of the compounds was performed based on in silico ADMET evaluation of the tested compounds. Screening results of drug-likeness rules showed that all compounds follow the accepted rules, meet the criteria of drug-likeness and follow Lipinski's rule of five. In addition, the toxicity results showed that all compounds are nonmutagenic and noncarcinogenic.
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http://dx.doi.org/10.1186/s13065-018-0479-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768023PMC
November 2018

Design, synthesis, in silico and in vitro antimicrobial screenings of novel 1,2,4-triazoles carrying 1,2,3-triazole scaffold with lipophilic side chain tether.

Chem Cent J 2017 Nov 21;11(1):117. Epub 2017 Nov 21.

Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah, 30002, Saudi Arabia.

Background: 1,2,4-Triazoles and 1,2,3-triazoles have gained significant importance in medicinal chemistry.

Results: This study describes a green, efficient and quick solvent free click synthesis of new 1,2,3-triazole-4,5-diesters carrying a lipophilic side chain via 1,3-dipolar cycloaddition of diethylacetylene dicarboxylate with different surfactant azides. Further structural modifications of the resulting 1,2,3-triazole diesters to their corresponding 1,2,4-triazole-3-thiones via multi-step synthesis has been also investigated. The structures of the newly designed triazoles have been elucidated based on their analytical and spectral data. These compounds were evaluated for their antimicrobial activities. Relative to the standard antimicrobial agents, derivatives of 1,2,3-triazole-bis-4-amino-1,2,4-triazole-3-thiones were the most potent antimicrobial agents with compound 7d demonstrating comparable antibacterial and antifungal activities against all tested microorganisms. Further, the selected compounds were studied for docking using the enzyme, Glucosamine-6-phosphate synthase.

Conclusions: The in silico study reveals that all the synthesized compounds had shown good binding energy toward the target protein ranging from - 10.49 to - 5.72 kJ mol and have good affinity toward the active pocket, thus, they may be considered as good inhibitors of GlcN-6-P synthase.
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http://dx.doi.org/10.1186/s13065-017-0347-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696273PMC
November 2017
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