Publications by authors named "Meshal A Almehmadi"

3 Publications

  • Page 1 of 1

Novel scaffold hopping of potent benzothiazole and isatin analogues linked to 1,2,3-triazole fragment that mimic quinazoline epidermal growth factor receptor inhibitors: Synthesis, antitumor and mechanistic analyses.

Bioorg Chem 2020 10 23;103:104133. Epub 2020 Jul 23.

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

A series of benzothiazole/isatin linked to 1,2,3-triazole moiety and terminal sulpha drugs 5a-e and 6a-e were synthesized and evaluated for cytotoxic activity against a panel of cancer cell lines. The novel compounds showed variable IC range of activity and some of them were potent compared to reference drug. The promising compounds were subjected as postulated the mimicry proposal for quinazoline-based EGFR inhibitors for their inhibitory profile against EGFR TK enzyme. That data obtained revealed that most of these compounds were potent EGFR TK inhibitors at nanomolar concentrations. Among these, compounds 5a and 5b showed more potent activity on EGFR compared to erlotinib (IC 103 and 104 versus 67.6 nM). Based upon the results, molecular docking analysis was performed on EGFR receptor and proved the strong contribution of fragments; benzothiazole, isatin, and triazole to the binding ATP pocket. When these selected compounds 5a and 5b were tested in an HepG2 model, they could effectively inhibited tumor growth, strongly induced cancer cell apoptosis, and suppressed cell cycle progression leading to DNA fragmentation. Well-DMET profile of the most active derivatives was presented and compared to the reference drugs. Taken together, we introduced novel triazole-sulpha drug hybrid for the first time as EGFR inhibitors and the results of our studies indicate that the newly discovered inhibitors have significant potential for anticancer treatment.
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http://dx.doi.org/10.1016/j.bioorg.2020.104133DOI Listing
October 2020

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

Synthesis and crystal structure of a new pyridinium bromide salt: 4-methyl-1-(3-phen-oxy-prop-yl)pyridinium bromide.

Acta Crystallogr E Crystallogr Commun 2017 Dec 3;73(Pt 12):1831-1834. Epub 2017 Nov 3.

Department of Chemistry, Taibah University, 30002, Al-Madina Al-Mounawara, Saudi Arabia.

In the cation of the title mol-ecular salt, CHNO·Br, the pyridinium and phenyl rings are inclined to one another by 11.80 (8)°. In the crystal, the Br anion is linked to the cation by a C-H⋯Br hydrogen bond. The cations stack along the -axis direction and are linked by further C-H⋯Br inter-actions, and offset π-π inter-actions [inter-centroid distances = 3.5733 (19) and 3.8457 (19) Å], forming slabs parallel to the plane. The effects of the C-H⋯ inter-action on the NMR signals of the and pyridinium protons in a series of related ionic liquids, . 4-methyl-1-(4-phen-oxy-but-yl)pyridin-1-ium salts, are reported and discussed.
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http://dx.doi.org/10.1107/S2056989017015481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730234PMC
December 2017
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