Consolidated antimicrobial and anticancer activities through newly synthesized novel series of pyrazoles bearing indazolylthiazole moiety: characterization and molecular docking

El‐Fakharany, Esmail M.; Dawoud, Nadia T. A.; El‐Gendi, Hamada; Emara, Abdallah; Lottfy, Doaa

doi:10.21608/ejchem.2021.83623.4104

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…Molecular docking as carried out against VEGFR-2 (ID: 4ASD) using the Molecular Operating Environment (MOE) 2014 software [ 72 , 73 , 74 , 75 , 76 ]. The Supplementary data provides further detailed information about the study.…”

Section: Methodsmentioning

confidence: 99%

Modified Benzoxazole-Based VEGFR-2 Inhibitors and Apoptosis Inducers: Design, Synthesis, and Anti-Proliferative Evaluation

et al. 2022

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This work is one of our efforts to discover potent anticancer agents. We modified the most promising derivative of our previous work concerned with the development of VEGFR-2 inhibitor candidates. Thirteen new compounds based on benzoxazole moiety were synthesized and evaluated against three human cancer cell lines, namely, breast cancer (MCF-7), colorectal carcinoma (HCT116), and hepatocellular carcinoma (HepG2). The synthesized compounds were also evaluated against VEGFR-2 kinase activity. The biological testing fallouts showed that compound 8d was more potent than standard sorafenib. Such compound showed IC50 values of 3.43, 2.79, and 2.43 µM against the aforementioned cancer cell lines, respectively, compared to IC50 values of 4.21, 5.30, and 3.40 µM reported for sorafenib. Compound 8d also was found to exert exceptional VEGFR-2 inhibition activity with an IC50 value of 0.0554 μM compared to sorafenib (0.0782 μM). In addition, compound 8h revealed excellent cytotoxic effects with IC50 values of 3.53, 2.94, and 2.76 µM against experienced cell lines, respectively. Furthermore, compounds 8a and 8e were found to inhibit VEGFR-2 kinase activity with IC50 values of 0.0579 and 0.0741 μM, exceeding that of sorafenib. Compound 8d showed a significant apoptotic effect and arrested the HepG2 cells at the pre-G1 phase. In addition, it exerted a significant inhibition for TNF-α (90.54%) and of IL-6 (92.19%) compared to dexamethasone (93.15%). The molecular docking studies showed that the binding pattern of the new compounds to VEGFR-2 kinase was similar to that of sorafenib.

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Section: Methodsmentioning

confidence: 99%

Modified Benzoxazole-Based VEGFR-2 Inhibitors and Apoptosis Inducers: Design, Synthesis, and Anti-Proliferative Evaluation

et al. 2022

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“…2D and 3D interactions between the conformers and the binding site of the enzyme were obtained. [66][67][68]…”

Section: Molecular Dockingmentioning

confidence: 99%

New Series of VEGFR-2 Inhibitors and Apoptosis Enhancers: Design, Synthesis and Biological Evaluation

Abdallah¹,

RR²,

Elnagar³

et al. 2022

DDDT

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Background: Cancer is still a major world health threat, causing a high rate of mortality. VEGFR-2 inhibitor anticancer agents are of great significance. However, they showed some serious side effects. Purpose: To discover new effective and safer anticancer agents, a new series of piperazinylquinoxaline-based derivatives was designed and synthesized on the basis of the pharmacophoric features of VEGFR-2 inhibitor drugs. Methods: The new candidates were evaluated against A549 lung cancer cells, HepG-2 hepatoma cells, Caco-2 colon cancer cells, MDA breast cancer cells, and VEGFR-2 kinase. Moreover, cell cycle kinetics and apoptosis rates were studied in HepG-2 cells treated with compound 11, which was the most promising candidate. Results: The new derivatives revealed better antitumor results (IC 50 from 6.48 to 38.58 µM) against the aforementioned cancer cell lines than sorafenib. Also, the new candidates showed VEGFR-2 inhibition with IC 50 values ranging from 0.19 to 0.60 µM compared to 0.08 µM for sorafenib. Compound 11, meanwhile, showed IC 50 values equal to 10. 61, 9.52, 12.45, 11.52, and 0.19 µM against the cancer cell lines and VEGFR-2, respectively. Moreover, compound 11 raised the apoptosis rate in HepG-2 cells from 5% to 44% and caused 4, 2.3, and 3-fold increases in BAX/Bcl-2 ratio, caspase-3 level, and P53 expression, respectively, compared to control untreated cells. Finally, the new derivatives displayed the correct binding mode into VEGFR-2 kinase pocket, giving interactions with the essential residues. Conclusion: This work suggests that compound 11 is a very significant anticancer candidate, and piperazinylquinoxaline is an important scaffold in the development of new potential effective and safer VEGFR-2 inhibitor agents.

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Spots on 1H‐Indazole Incorporation into Thiazole Moiety‐Hybrid Heterocycles, Strong Efficacy as Small Molecules with Antimicrobial, Antineoplastic Activity, and In‐Silico Studies

Dawoud,

El‐Gendi,

Lotfy

et al. 2024

ChemistrySelect

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Amidst the escalating cancer cases and the relentless spread of multidrug‐resistant microbes, the urgency for effective medication is undeniable. In this context, our lab's continuous efforts have led to a promising discovery. We have conducted an extensive study on a series of new heterocycles with an indazolylthiazole component, which holds great promise as antimicrobial and anticancer drugs. The bioactivity tests, conducted with meticulous methodology, have demonstrated that the synthesized compounds possess remarkable antibacterial activity against various pathogenic strains. In a controlled lab setting, we have observed that derivatives 9, 11, and 12a effectively induce apoptosis in HCT‐166 and Huh‐7 (liver carcinoma) cell lines. Among these, derivative 11 has shown the highest selectivity (SI=14.54±1.2 and 16.51±1.4) and the lowest IC50 value. These compounds also exhibit broad‐spectrum antimicrobial activity. The anticancer activity of the synthesized compounds has been computationally confirmed through molecular modeling using MOE software and pharmacokinetic studies. Most of the tested compounds have shown significant cytotoxic activity against tumor cell lines, with high safety against normal human cells, thereby paving the way for a hopeful and promising future of antimicrobial and anticancer drugs, with potential applications in [specific_application_1] and [specific_application_2].

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Consolidated antimicrobial and anticancer activities through newly synthesized novel series of pyrazoles bearing indazolylthiazole moiety: characterization and molecular docking

Cited by 4 publications

References 26 publications

Modified Benzoxazole-Based VEGFR-2 Inhibitors and Apoptosis Inducers: Design, Synthesis, and Anti-Proliferative Evaluation

Modified Benzoxazole-Based VEGFR-2 Inhibitors and Apoptosis Inducers: Design, Synthesis, and Anti-Proliferative Evaluation

New Series of VEGFR-2 Inhibitors and Apoptosis Enhancers: Design, Synthesis and Biological Evaluation

Spots on 1H‐Indazole Incorporation into Thiazole Moiety‐Hybrid Heterocycles, Strong Efficacy as Small Molecules with Antimicrobial, Antineoplastic Activity, and In‐Silico Studies

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