Synthesis, modeling, and biological studies of new thiazole-pyrazole analogues as anticancer agents

Ashour, Gadeer R. S.; Qarah, Ahmad Fawzi; Alrefaei, Abdulmajeed F.; Alalawy, Adel I.; Alsoliemy, Amerah; Alqahtani, Alaa M.; Al-Amoudi, Wael M.; El‐Metwaly, Nashwa M.

doi:10.1016/j.jscs.2023.101669

Cited by 7 publications

(4 citation statements)

References 72 publications

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“…Aiming to improve the anticancer properties of pyrazole-thiazole hybrids and encouraged by the promising activities of N-phenylpyrazole-thiazole hybrid (A) [14], new N-phenylpyrazolone-N-benzylthiazole hybrids (3)(4)(5)(6) were designed according to the chemicals available in our feedstock, employing variation of substituents and bioisostere strategies (Figure 4). Thereafter and for comparison with A, starting compound 1 and the target molecules 3-6 (as numbered in the organic synthesis part) were sketched and in silico evaluated to predict their physicochemical features and drug-like nature (Table 1) through the free ADMETlab 2.0 online platform [22,23].…”

Section: Design Strategymentioning

confidence: 99%

“…[8][9][10][11][12][13]. Recently, literature proved that pyrazole-hybrid thiazoles (A-C) are potent bioactive small molecules endowed with distinct biochemical activities, including anticancer [14,15] and antimicrobial agents [16,17] as well as carbonic anhydrase inhibitors [18] (Figure 3). Consequently, the construction of new bioactive pyrazole-thiazole hybrids is an attractive target for organic and medicinal chemists.…”

Section: Introductionmentioning

confidence: 99%

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New edaravone analogs incorporated with N‐benzylthiazole moiety: Multistep chemical synthesis, in vitro cytotoxicity with pRIPK3 inhibitory activities, and molecular docking

Ahmed,

El‐All,

El‐Hallouty

et al. 2024

Journal of Heterocyclic Chem

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In this research article, the chemical synthesis of new N‐phenylpyrazolone‐N‐benzylthiazole hybrids (3–6) via late‐stage thiazolation of the corresponding benzylthiosemicarbazone 2 was reported. The skeletal structural of the new molecules were validated by instrumental measurements (FT‐IR, NMR, and EI‐MS). In vitro cytotoxicity‐based cellular MTT bioassay shows that compound 3 that bears an N‐benzyl‐4‐thiazolone moiety is the most potent one toward the osteosarcoma cell line (Hos) with an IC50 value of 5.8 ± 0.1 μM, while compound 4a that contains a 5‐acetyl‐N‐benzylthiazole unit is the most robust one against the model lung carcinoma cell line (A549) with an IC50 value of 9.23 ± 0.01 μM. Also, 3 is roughly equipotent to 4b in its cytotoxicity activity against A549. In vitro enzymatic ELISA bioassay of A549 cells indicates that IC50 of 3 caused a decrease in the pRIPK3 kinase concentration (2.89 ± 0.005 pg/mL) as compared to DMSO‐treated cells (2.93 ± 0.010 pg/mL), while the pRIPK3 level incresed with 4b impact. As a result, 3 may be an effective inhibitor of pRIPK3 and hence necroptosis, proposing a novel therapeutic strategy for necroptosis‐related illnesses. In silico molecular docking shows that 3 interlocked and fitted well into the binding site of RIPK3 (PDB code: 7MX3) with a fitness value (−123.382 kcal/mol) lower than 4b and forms an important H‐bond with Lys50 like the marketed RIPK3 inhibitor GSK'843, validating the experimental results. Consequently, 3 is the most promising molecule that could be a lead candidate for further studies.

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Section: Design Strategymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New edaravone analogs incorporated with N‐benzylthiazole moiety: Multistep chemical synthesis, in vitro cytotoxicity with pRIPK3 inhibitory activities, and molecular docking

Ahmed,

El‐All,

El‐Hallouty

et al. 2024

Journal of Heterocyclic Chem

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“…The thiazole ring is very useful in terms of biological activity. There is a lot of literature information showing its anticancer and antifungal activity [10–17] . In addition to this information, there is also a study using the thiazole ring as a VEGFR‐2 inhibitor [18] .…”

Section: Introductionmentioning

confidence: 99%

“…There is a lot of literature information showing its anticancer and antifungal activity. [10][11][12][13][14][15][16][17] In addition to this information, there is also a study using the thiazole ring as a VEGFR-2 inhibitor. [18] When docking studies are examined, the interaction of the thiazole ring with Asp1046, which is an important amino acid for the enzyme, shows the potential of the ring to inhibit VEGFR-2.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Imidazole‐2,3‐dihydrothiazole Compounds as VEGFR‐2 Inhibitors and Their Support with in Silico Studies

Osmaniye,

Bozkurt,

Kurban

et al. 2023

Chemistry & Biodiversity

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When the structure of VEGFR inhibitors is examined, it is seen that it consists of 4 pharmacophoric parts. In the light of this information, within the scope of this study, new 2‐((1‐(4‐(1H‐imidazol‐1‐yl)phenyl)ethylidene)hydrazineylidene)‐3‐ethyl‐4‐(substitutephenyl)‐2,3‐dihydrothiazole derivatives were synthesized. Structure determinations of the synthesized derivatives were made using spectroscopic methods. Firstly, the resulting compounds (4a‐4l) were subjected to the 24‐hour MTT test against MCF7, HepG2 and NIH3T3 cells. According to the MTT test results, compound 4h showed activity with IC50=4.566±0.246 µM and compound 4k with IC50=4.537±0.463 µM against HepG2 cell line. The antifungal activities and biofilm inhibition percentages of all compounds against infection problems that may develop in patients receiving chemotherapy were investigated. Compounds 4h and 4k which are active in the MTT test were tested for inhibition of VEGFR‐2 enzymes. Compound 4h displayed VEGFR‐2 inhibition with IC50=0.066±0.002 µM value; compound 4k did not show enzyme inhibition with an IC50>10 µM. Molecular docking studies were performed with two compounds (4k and 4h) and sorafenib to understand the dramatic difference for VEGFR‐2 inhibition. Molecular dynamics studies were performed with using 4h‐4ASE complex and both stability (RMSD, RMSF, Rg) and interaction potentials of the complex were analyzed and presented.

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Molecular modeling and antimicrobial activity of newly synthesized benzothiazole-thiazole conjugates

Alharbi,

Alsahag,

Alisaac

et al. 2024

Journal of Photochemistry and Photobiology A: Chemistry

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Synthesis, modeling, and biological studies of new thiazole-pyrazole analogues as anticancer agents

Cited by 7 publications

References 72 publications

New edaravone analogs incorporated with N‐benzylthiazole moiety: Multistep chemical synthesis, in vitro cytotoxicity with pRIPK3 inhibitory activities, and molecular docking

New edaravone analogs incorporated with N‐benzylthiazole moiety: Multistep chemical synthesis, in vitro cytotoxicity with pRIPK3 inhibitory activities, and molecular docking

Synthesis of Imidazole‐2,3‐dihydrothiazole Compounds as VEGFR‐2 Inhibitors and Their Support with in Silico Studies

Molecular modeling and antimicrobial activity of newly synthesized benzothiazole-thiazole conjugates

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