Synthesis and antiproliferative activity studies of new functionalized pyridine linked thiazole derivatives

Alqahtani, Alaa M.; Bayazeed, Abrar

doi:10.1016/j.arabjc.2020.11.020

Cited by 41 publications

(14 citation statements)

References 44 publications

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“…[29] ROCK-1 is critical for cancer cell migration and invasion, revealing it may be useful therapeutic target. [30] Their binding energies, conventional hydrogen bonds and the closest interacting residues with active sites are summarized below (Table 5).…”

Section: Molecular Docking Analysis 2421 Binding Energies Of the Synthesized Compoundsmentioning

confidence: 99%

Synthesis, Structure‐Activity Relationship and in silico Studies of Novel Pyrazolothiazole and Thiazolopyridine Derivatives as Prospective Antimicrobial and Anticancer Agents

et al. 2021

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In our attempt to develop potential new drug candidates with promising dual antimicrobial and anticancer activities, a series of pyrazolothiazole and thiazolopyridine analogues has been synthesized. All compounds were evaluated for their antimicrobial potential towards pathogenic strains and cytotoxicity properties against hepatic cancer cell line HepG-2 and breast cancer cell line MCF-7. 9 c showed excellent antimicrobial activity against the tested strains, with MIC values about 27.5 μM (S. epidermidis), 6.8 (B. subtilis) and 3.4 μM (S. pneumoniae and K. pneumoniae) fold higher than the reference drug, whilst 9 a, 9 b and 5 a exhibited also potent activity against selected strains. Moreover, compounds 9 c (IC50 = 10.89 μM and 15.60 μM) and 9 a (IC50 = 22.24 μM and 28.47 μM) showed promising anticancer activity for HepG2 and MCF-7 cell lines, respectively, when compared to the known anticancer drugs, 5-Fluorouracil (IC50 = 26.75 μM and IC50 = 32.75 μM). The data from structure-activity relationships analysis revealed the potency of pyrazolothiazole than thiazolopyridine derivatives in generating potential activity. Further, molecular docking studies performed on the more active antimicrobial and cytotoxic compound, 9 c to get insights for binding modes to the target enzymes (PDB ID: 1JIJ) for antimicrobial, and (PDB ID: 1DI8) and (PDB ID: 3TWJ) for anticancer revealed that they interacted with the same key amino acids with TyrRS for S. aureus, CDK2 and ROCK1, respectively.

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Section: Molecular Docking Analysis 2421 Binding Energies Of the Synthesized Compoundsmentioning

confidence: 99%

Synthesis, Structure‐Activity Relationship and in silico Studies of Novel Pyrazolothiazole and Thiazolopyridine Derivatives as Prospective Antimicrobial and Anticancer Agents

et al. 2021

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“…[46] While, transformation of pyrazolyl-thiophene compound 3 to pyrazolo [3,4-d]thieno [3,2-b]pyridines 5a-c increased the cytotoxic activity toward HepG2 and PC3 cancer cell lines. The activity of compound 5c (IC 50 = 4.08 μM), substituted by the chromophore 4-chlorophenyl group [47] at pyridine ring, is higher than the standard anticancer drug Doxorubicin that exhibit potency with IC 50 value 4.58 μM against HepG2 cancer cell line. Interestingly, the insertion of thiazole skeleton [48] to the pyrazolylthiophene compound via double bond linkage as in compounds 6 and 7 produced a selective enhancement of the [3,2-b]pyridines 10a-c improved the anticancer potency especially against HepG2 and PC3 cancer cell lines.…”

Section: Structure-activity Relationshipmentioning

confidence: 94%

Convenient synthesis and anticancer evaluation of novel pyrazolyl‐thiophene, thieno[3,2‐b]pyridine, pyrazolo[3,4‐d]thieno[3,2‐b]pyridine and pyrano[2,3‐d]thieno[3,2‐b]pyridine derivatives

Masaret

2021

Journal of Heterocyclic Chem

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The newly synthesized 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl) thiophen-2-yl)-3-oxopropanoate was utilized as a precursor for the synthesis of pyrazolyl-thiophene derivative, which undergoes cyclization upon treatment with benzaldehyde derivatives to provide pyrazolo [3,4-d]thieno[3,2-b]pyridines. Basic treatment of pyrazolyl-thiophene derivative with phenyl isothiocyanate followed by subsequent addition of chloroacetone and/or ethyl bromoacetate yielded the thiazolylidene-pyrazolyl thiophenes. In addition, the building block 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was converted into the corresponding thieno[3,2-b] pyridine compounds through its reactions with (DMF-DMA) and/or heating in sodium ethoxide. Moreover, the reaction of 7-hydroxy-5-oxo-N-phenyl-2-(phenylamino)-4,5-dihydrothieno[3,2-b]pyridine-3-carboxamide with 2-arylidenemalononitrile produced the new annulated pyrano[2,3-d]thieno[3,2-b]pyridines. The prepared thiophene-based compounds were evaluated against HepG2, PC3, and MCF-7 cancer cells, and normal fibroblast cell (WI38). The pyrazolo [3,4-d]thieno[3,2-b]pyridine and pyrano [2,3-d]thieno[3,2-b]pyridine compounds substituted with chlorophenyl group presented promising cytotoxic activities against HepG2 cancer cell line without any human toxicity. Docking study for the synthesized thiophene compounds delivered valuable insights about the binding interactions with the crystal structure of NS5B enzyme with PDB ID (4TLR).

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“…The synthesized compounds were subjected to the MTT cytotoxicity assay on the basis of the cited literature 41 .…”

Section: Methodsmentioning

confidence: 99%

Synthesis and biological screening of new thiadiazolopyrimidine-based polycyclic compounds

Alqahtani

2021

Sci Rep

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Novel tri-and tetra-cyclic compounds based on the thiadiazolopyrimidine ring system were synthesized, and their antimicrobial activity was estimated. The obtained results evidenced the substantial efficiencies of pyrano-thiadiazolopyrimidine compounds 8a–b and 9a–b toward the two strains of gram-positive bacteria (S. aureus and B. cereus). Besides, tetracyclic pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a–b and 17a–b displayed prominent efficiencies toward the two strains of gram-negative bacteria (E. coli and P. aeruginosa). In addition, compounds 8a–b and 9a–b displayed good efficacy toward C. albicans. The activity of antiquorum sensing (anti-QS) inhibition of the newly synthesized thiadiazolopyrimidine-based compounds toward C. violaceum was tested, suggesting satisfactory activity for derivatives 16a–b, 17a–b, 8b, and 9a. The cytotoxic activity of these derivatives was screened toward various cancer cell lines (MCF-7, PC3, Hep-2, and HepG2) and standard normal fibroblast cells (WI38) by utilizing the MTT assay. The pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a, 16b17a, and 17b showed potent cytotoxic efficacy against the MCF-7 cells with the IC50 values ranging from 5.69 to 9.36 µM. Also, the endorsed structural activity relationship (SAR) of the inspected thiadiazolopyrimidine derivatives provided a correlation between the chemical structure and anticancer efficiency. The in silico docking studies were implemented for silencing the hormonal signaling in the breast (PDB Code-5NQR). The results were found to be consistent with the cytotoxic activity.

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Synthesis and antiproliferative activity studies of new functionalized pyridine linked thiazole derivatives

Cited by 41 publications

References 44 publications

Synthesis, Structure‐Activity Relationship and in silico Studies of Novel Pyrazolothiazole and Thiazolopyridine Derivatives as Prospective Antimicrobial and Anticancer Agents

Synthesis, Structure‐Activity Relationship and in silico Studies of Novel Pyrazolothiazole and Thiazolopyridine Derivatives as Prospective Antimicrobial and Anticancer Agents

Convenient synthesis and anticancer evaluation of novel pyrazolyl‐thiophene, thieno[3,2‐b]pyridine, pyrazolo[3,4‐d]thieno[3,2‐b]pyridine and pyrano[2,3‐d]thieno[3,2‐b]pyridine derivatives

Synthesis and biological screening of new thiadiazolopyrimidine-based polycyclic compounds

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