Design, synthesis and docking studies of new hydrazinyl-thiazole derivatives as anticancer and antimicrobial agents

El‐Naggar, Abeer M.; Zidan, Alaa; Taghour, Mohammed S; Badawi, Waleed A.

doi:10.1016/j.jscs.2022.101488

Cited by 19 publications

(4 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results indicate that the anti-proliferative activity of compound 4 could be attributed to its ability to induce programmed cell death by effectively arresting MCF-7 cells at the pre-G1 phase of the cell cycle while decreasing the cellular population in the G2/M phase. These results are in agreement with previous studies, which showed that 1,3-thiazoles cause cell cycle arrest in HepG2 cells at the S and pre-G1 phases [ 17 , 63 , 64 , 65 ].…”

Section: Resultssupporting

confidence: 94%

Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Study

et al. 2022

View full text Add to dashboard Cite

Breast cancer is the most common cancer in women, responsible for over half a million deaths in 2020. Almost 75% of FDA-approved drugs are mainly nitrogen- and sulfur-containing heterocyclic compounds, implying the importance of such compounds in drug discovery. Among heterocycles, thiazole-based heterocyclic compounds have demonstrated a broad range of pharmacological activities. In the present study, a novel set of 1,3-thiazole derivatives was designed and synthesized based on the coupling of acetophenone derivatives, and phenacyl bromide was substituted as a key reaction step. The activity of synthesized compounds was screened against the proliferation of two breast cancer cell lines (MCF-7 and MDA-MB-231). Almost all compounds exhibited a considerable antiproliferative activity toward the breast cancer cells as compared to staurosporine, with no significant cytotoxicity toward the epithelial cells. Among the synthesized compounds, compound 4 exhibited the most potent antiproliferative activity, with an IC50 of 5.73 and 12.15 µM toward MCF-7 and MDA-MB-231 cells, respectively, compared to staurosporine (IC50 = 6.77 and 7.03 µM, respectively). Exploring the mechanistic insights responsible for the antiproliferative activity of compound 4 revealed that compound 4 possesses a significant inhibitory activity toward the vascular endothelial growth factor receptor-2 (VEGFR-2) with (IC50 = 0.093 µM) compared to Sorafenib (IC50 = 0.059 µM). Further, compound 4 showed the ability to induce programmed cell death by triggering apoptosis and necrosis in MCF-7 cells and to induce cell cycle arrest on MCF-7 cells at the G1 stage while decreasing the cellular population in the G2/M phase. Finally, detailed in silico molecular docking studies affirmed that this class of compounds possesses a considerable binding affinity toward VEGFR2 proteins. Overall, these results indicate that compound 4 could be a promising lead compound for developing potent anti-breast cancer compounds.

show abstract

Section: Resultssupporting

confidence: 94%

Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Study

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Thiazoles (Ayati et al, 2019; Ewida et al, 2017; Hassan et al, 2020; Pawar et al, 2021; de Santana et al, 2018; Sayed et al, 2020; Sharma et al, 2020) caught the attention of medicinal chemists due to their potential anticancer properties. Thiazole is a crucial scaffold for several antitumor agents targeting VEGFR‐2 (Al‐Warhi et al, 2022; El‐Naggar et al, 2022; Hassan et al, 2021). Also, dabrafenib (Puszkiel et al, 2019), dasatinib (Keating, 2017), and masitinib (Dubreuil et al, 2009) (Figure 4) are FDA‐approved drugs that contain thiazole scaffold and selectively inhibit tyrosine kinase receptors with very strong antitumor activity.…”

Section: Design Strategymentioning

confidence: 99%

“…Thiazole is a crucial scaffold for several antitumor agents targeting VEGFR-2 (Al-Warhi et al, 2022;El-Naggar et al, 2022;Hassan et al, 2021). Also, dabrafenib (Puszkiel et al, 2019), dasatinib (Keating, 2017), and masitinib (Dubreuil et al, 2009) (Figure 4) are FDA-approved drugs that contain thiazole scaffold and selectively inhibit tyrosine kinase receptors with very strong antitumor activity.…”

Section: Design Strategymentioning

confidence: 99%

Design, synthesis, and antitumor screening of new thiazole, thiazolopyrimidine, and thiazolotriazine derivatives as potent inhibitors of VEGFR‐2

Abd Elhameed,

Ali,

Ghabbour

et al. 2023

Drug Development Research

View full text Add to dashboard Cite

New thiazole, thiazolopyrimidine, and thiazolotriazine derivatives 3–12 and 14a–f were synthesized. The newly synthesized analogs were tested for in vitro antitumor activity against HepG2, HCT‐116, MCF‐7, HeP‐2, and Hela cancer cells. Results indicated that compound 5 displayed the highest potency toward the tested cancer cells. Compound 11b possessed enhanced effectiveness over MCF‐7, HepG2, HCT‐116, and Hela cancer cells. In addition, compounds 4 and 6 showed promising activity toward HCT‐116, MCF‐7, and Hela cancer cells and eminent activity against HepG2 and HeP‐2 cells. Moreover, compounds 3–6 and 11b were tested for their capability to inhibit vascular endothelial growth factor receptor‐2 (VEGFR‐2) activity. The obtained results showed that compound 5 displayed significant inhibitory activity against VEGFR‐2 (half‐maximal inhibitory concentration [IC50] = 0.044 μM) comparable to sunitinib (IC50 = 0.100 μM). Also, the synthesized compounds 3–6 and 11b were subjected to in vitro cytotoxicity tests over WI38 and WISH normal cells. It was found that the five tested compounds displayed significantly lower cytotoxicity than doxorubicin toward normal cell lines. Cell cycle analysis proved that compound 5 induces cell cycle arrest in the S phase for HCT‐116 and Hela cancer cell lines and in the G2/M phase for the MCF‐7 cancer cell line. Moreover, compound 5 induced cancer cell death through apoptosis accompanied by a high ratio of BAX/BCL‐2 in the screened cancer cells. Furthermore, docking results revealed that compound 5 showed the essential interaction bonds with VEGFR‐2, which agreed with in vitro enzyme assay results. In silico studies showed that most of the analyzed compounds complied with the requirements of good oral bioavailability with minimal toxicity threats in humans.

show abstract

“…At present, researchers are interested in molecular hybridization, which is considered one of the important branches of pharmaceutical chemistry. For example, thiazole-thiophene hybrids, often have improved pharmacodynamic and pharmacokinetic behavior compared to if each unit was used separately [21,24]. Furthermore, Ensaf and Mohareb demonstrated the synthesis of thiazoles, pyrans and pyridines from 1,3-diketones [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of bioactive heterocyclic compounds using camphor

Sultan Alwan,

Milad Mohareb

2024

Bull. Chem. Soc. Eth.

View full text Add to dashboard Cite

The aim of the work was to synthesize novel heterocyclic compounds derived from camphor with antibacterial activity. The pyridazine, xanthene, pyranothiazole, pyridinothiazole, thiophene and pyrazole derivatives were produced from 4,11,11-trimethyl-9-phenyl-7-(2-phenylhydrazono)-3,4,5,6,7,9-hexahydro-1H-1,4-methanoxanthen-8(2H)-one (1). Thiophene derivatives 6a,b were produced according to the Gewald’s reaction for thiophene synthesis. On the other hand, pyranothiazol derivatives 8a,b were synthesized by the multicomponent reactions between xanthene derivative 5, benzaldehyde and ethylcyanoacetate or malononitrile in ethanol/triethylamine. Whereas, pyridinothiazole derivative 9 was produced in ethanol/ammonium acetate by the multicomponent reaction between xanthene derivative 5, benzaldehyde and malononitrile. The antibacterial activity of the synthesized compounds was evaluated against E. coli bacteria. All synthesized compounds showed moderate activity against E. coli bacteria. KEY WORDS: Anti-microbial, Camphor, Heterocyclic, Pyrazol-3(2H)-one, Thiazol-4(5H)-one, Thieno[3,2-d]thiazole, Xanthenes Bull. Chem. Soc. Ethiop. 2024, 38(4), 1069-1076. DOI: https://dx.doi.org/10.4314/bcse.v38i4.20

show abstract

Design, synthesis and docking studies of new hydrazinyl-thiazole derivatives as anticancer and antimicrobial agents

Cited by 19 publications

References 42 publications

Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Study

Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Study

Design, synthesis, and antitumor screening of new thiazole, thiazolopyrimidine, and thiazolotriazine derivatives as potent inhibitors of VEGFR‐2

Synthesis of bioactive heterocyclic compounds using camphor

Contact Info

Product

Resources

About