Evaluation of 6-chloro-N-[3,4-disubstituted-1,3-thiazol-2(3H)-ylidene]-1,3-benzothiazol-2-amine Using Drug Design Concept for Their Targeted Activity Against Colon Cancer Cell Lines HCT-116, HCT15, and HT29

Zhu, Maguang; Wang, Cui-Yue; Xu, Cheng-Mian; Bi, Weiping; Zhou, Xifa

doi:10.12659/msm.899646

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…In both pyrazolo[1,5-c] quinazolin-2-one (class A) and 2-methylquinazolin-4(3H)-one (class B) derivatives, chloro-substituted molecules (compounds IXa and XIIIa) were found to fit better in the active site of the receptor than those with nitro substituents (compounds IXb and XIIIb). This is consistent with previously reported results that halogen derivatives mostly fit better in the active site of the EGFR enzyme ( 32 ).…”

Section: Discussionsupporting

confidence: 94%

Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents

et al. 2022

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Background and purpose: In this study, some new cytotoxic hybrid structures were synthesized by combining pyrazolinone and imidazolinone rings with quinazoline pharmacophores. Experimental approach: The benzoxazinone, pyrazolo-quinazoline fused ring, and imidazolinone anchored quinazoline derivatives were synthesized by simple ring-opening, ring expansion, and ring closure strategies from oxazolones. The molecular docking studies of the final derivatives were accomplished on the epidermal growth factor receptor enzyme. The cytotoxic effect of the final compounds on the MCF-7 cell line was evaluated by MTT assay. Findings/Results: The docking results confirmed the optimized electrostatic, H-bonding, and hydrophobic interactions of structures with the key residues of the active site (ΔG bin < -9Kcal/mol). The derivatives have been obtained in good yield and purity, and their structures were confirmed by different methods (FT-IR, 1 H-NMR, 13 C-NMR, and CHNS analysis). The IC 50 s of all final derivatives against the MCF-7 cell line were lower than 10 μM, and between all, the IXa from pyrazolo-quinazolinone class (IC 50 : 6.43 μM) with chlorine substitute was the most potent. Furthermore, all derivatives showed negligible cytotoxicity on HUVEC normal cell line which would be a great achievement for a novel cytotoxic agent. Conclusion and implications: Based on the obtained results, pyrazolo[1,5-c] quinazolin-2-one series were more cytotoxic than imidazolinone methyl quinazoline-4(3H)-ones against MCF-7 cells. Chlorine substitute in the para position of the aromatic ring improved the cytotoxicity effect in both classes. It could be related to the polarizability of a chlorine atom and making better intermolecular interactions. Further pre-clinical evaluations are required for the promising synthesized cytotoxic compounds.

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Section: Discussionsupporting

confidence: 94%

Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents

et al. 2022

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“…These results come after the good electronegativity profile due to the chloro substitution which strengthens bonds to the receptor. A study of the structure-activity relationship (SAR) showed the ligand better biological activity by electron-withdrawing group substitution for they can improve the lipophilicity and hydrogen interaction to the receptor ( 16 ). The chloro group also took part in the hydrogen bonds formation and contributed to the bond strengthening, even ranked better than clorobiocin and tetracycline as standards ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular docking, synthesis, and antibacterial activity of the analogs of 1-allyl-3-benzoylthiourea

Shalas,

Winarsih,

Ihsan

et al. 2023

Research in Pharmaceutical Sciences

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Background and purpose: The incidence of antibiotic resistance rapidly emerges over the globe. In the present study, the synthesis of thiourea derivatives as antibacterial agents and their biological evaluation are reported. Experimental approach: Preliminary studies were done by molecular docking of four analogs of 1-allyl-3-benzoylthiourea, clorobiocin, and ciprofloxacin on the DNA gyrase subunit B receptor (PDB: 1KZN). The nucleophilic substitution reaction of benzoyl chloride analogs to the allylthiourea yielded four 1-allyl-3-benzoylthiourea analogs (Cpd 1-4). The reactions were done by a modified Schotten Baumann method. The in vitro antimicrobial activities were determined using the agar dilution method against methicillin-resistant Staphylococcus aureus (MRSA), Salmonella typhi, Escherichia coli, and Pseudomonas aeruginosa. Findings/Results: The in-silico study showed that Cpd 1-4 possesses a good interaction on the DNA gyrase subunit B receptor compared to the ciprofloxacin. Cpd 3 had the best binding affinity with a rerank score of - 91.2304. Although the candidate compounds showed unsatisfactory antibacterial activity, they indicated an increasing trend of growth inhibition along with the increment of concentration. Cpd 1 and 4 exhibited in vitro antibacterial activities against MRSA with a minimum inhibitory concentration value of 1000 µg/mL, better compared to the other compounds. Conclusion and implication: Despite lacking antibacterial activity, all the synthesized compounds showed an increased trend of growth inhibition along with the increment of concentration. Therefore, additional development should be implemented to the compounds of interest in which optimization of lipophilicity and steric properties are suggested.

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The art of design in azlactone–benzoxazinone chemistry, docking studies and

et al. 2022

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In this study, by combining azlactone–benzoxazinone chemistry, we synthesized new hybrid compounds and evaluated the in vitro cytotoxicity on the breast cancer cell line. The desired compounds were synthesized using green and straightforward chemical reactions on azlactone and benzoxazinone structures through simple ring closure and nucleophilic ring-opening reactions. Preliminary in vitro cytotoxic results on the MCF-7 breast cancer cell line showed that the synthesized compounds have excellent anticancer activity with interestingly low inhibitory concentrations (IC50s in the range of 8–20 mM). Fortunately, our structures simultaneously had low toxicity on the normal HUVEC cell line. Finally, molecular docking studies were performed on the EGFR enzyme as one of the active signaling pathways in cancer cells for the best cytotoxic candidates. In this regard, the alignment of the docking and cytotoxicity results was interesting. In conclusion, these potential cytotoxic compounds could be considered in further studies.

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Evaluation of 6-chloro-N-[3,4-disubstituted-1,3-thiazol-2(3H)-ylidene]-1,3-benzothiazol-2-amine Using Drug Design Concept for Their Targeted Activity Against Colon Cancer Cell Lines HCT-116, HCT15, and HT29

Cited by 4 publications

References 26 publications

Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents

Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents

Molecular docking, synthesis, and antibacterial activity of the analogs of 1-allyl-3-benzoylthiourea

The art of design in azlactone–benzoxazinone chemistry, docking studies and

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