Molecular Docking Studies, Antiproliferative Evaluation, and Synthesis of 7-(1H-Indol-3-yl)pyrido[2,3-d]pyrimidine Derivatives

Radwan, Mohamed A. A.; Rugaie, Osamah Al; Abdulmonem, Waleed Al; Awad, H.; Zayed, Ehab M.

doi:10.1134/s1068162022040161

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…Singlet signal at δ 7.50 ppm assigned for one proton at C6 pyridine. 13 CNMR spectrum for the same compound revealed the presence of three characteristic signals at δ29.24, 167.16 and 170.78ppm assigned for C-2thiazolo, C-3 and C-5 carbonyl carbons respectively.…”

Section: Chemistrymentioning

confidence: 94%

“…Thus, EGFRs (wild and mutant types ) are interesting biological targets for the discovery of new anticancer agents. 11,12 Leads bearing pyrido [2,3-d]pyrimidine scaffold are considered interesting cores for their promising cytotoxic activity 13 , through inhibition of wild and mutant types of EGFR(Figure1). For example, the oxopyrido [2,3-d]pyrimidinyl derivative I [14] was reported as potent inhibitor of both mutant types of EGFR with 100−fold selectivity than the wild one.…”

Section: Introductionmentioning

confidence: 99%

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Novel Pyrido-Thiazolo-Pyrimidinone Hybrids targeting EGFRWT and EGFRT790M: Design, Synthesis, Anticancer Activity and docking simulation

Alasfoury

Nossier²,

El-Manawaty³

et al. 2023

Azhar International Journal of Pharmaceutical and Medical Scien

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Pyrido[2,pyrimidines and thiazolo based scaffold were reported to exhibit valuable anticancer activity and inhibit EGFR tyrosine kinase receptors wild and mutant types as well. So a new series of 6,8-diaryl pyrido [2,3-d]thiazolo[3,2-a]pyrimidinones 2a-c was synthesized and their confirmed chemical structures were established through various spectral analyses including IR, 1 HNMR, 13 CNMR and mass spectroscopy. Anticancer evaluation was performed through screening for these compounds against MCF-7, PC-3, HCT-116 and A-549 cancerous cell lines at a dose of 100 in comparison with erlotinib. The antiproliferative activity revealed that compound 2a was excellent and approximately equipotent with the reference (IC50= 13.25 and 11.05 μM) which implicated that substitution at position 6 and 8 greatly affect the cytotoxic activity. Furthermore, the promising compound 2a was subjected to molecular docking analysis against EGFR WT and EGFR T790M kinases to examine the binding mode and elucidate the mechanism of the promising cytotoxic activity. Finally compound 2a has been shown to be good candidate that deserve further investigation.

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Section: Chemistrymentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Novel Pyrido-Thiazolo-Pyrimidinone Hybrids targeting EGFRWT and EGFRT790M: Design, Synthesis, Anticancer Activity and docking simulation

Alasfoury

Nossier²,

El-Manawaty³

et al. 2023

Azhar International Journal of Pharmaceutical and Medical Scien

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Synthesis, Biological Evaluation, and Molecular Docking Studies of Indole‐Based Heterocyclic Scaffolds as Potential Antibacterial Agents

Khalaf,

Abdel‐Aziz,

Radwan

et al. 2024

Chemistry & Biodiversity

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Indole‐based heterocyclic scaffolds have become increasingly important in medicinal chemistry due to their notable pharmacological and biological properties. Their role in the discovery and development of innovative drugs for treating various diseases highlights their value. This study aimed to synthesize C3‐indole derivatives linked to various heterocyclic scaffolds, including thiophenes, thiazolidine‐4‐ones, and 1,3,4‐thiadiazoles, via the reaction of ethylthioacetanilide 2 with different α‐haloketones.The structures of the target compounds were established using 1H and 13C nuclear magnetic resonance spectroscopy, mass spectrometry, infrared spectroscopy, and elemental analysis. The synthesized compounds were tested for antimicrobial activity against different microbes: S. aureus ATCC 6538 (Gram‐positive bacteria), E. coli ATCC 25933 (Gram‐negative bacteria), C. albicans ATCC 10231 (yeast), and fungi (A. niger NRRL−A326). Thiophene 6a, thiazolidine‐4‐one 8, and compound 10d exhibited the highest antimicrobial activities. The molecular docking study showed that compounds 2, 4, 6a, and 6c had good binding energy and favorable binding modes of interactions with the DNA gyrase B enzymes (PDB: 3 U2D) and (PDB: 1S14). The results showed that the NH group of the indole in compounds 2 and 4, together with the nitrile group (CN), played an important role in inhibiting DNA gyrase B of S. aureus, PDB: 3 U2D. Furthermore, the NH of the indole ring, together with the ethylamino group of compound 2, was crucial in inhibiting DNA gyrase B of E. coli, PDB: 1S14. These findings may encourage researchers to develop more effective C3‐indole derivatives in their search for antimicrobial drugs.

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Investigation of bisindole-linked pyrimidine moieties: synthesis using strantium–aluminum supported strontium aluminate nanophosphors catalyst, DNA reactivity, and in silico molecular docking studies

Hanumesh,

Amshumali,

Prachi

et al. 2024

Nucleosides, Nucleotides & Nucleic Acids

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Molecular Docking Studies, Antiproliferative Evaluation, and Synthesis of 7-(1H-Indol-3-yl)pyrido[2,3-d]pyrimidine Derivatives

Cited by 4 publications

References 34 publications

Novel Pyrido-Thiazolo-Pyrimidinone Hybrids targeting EGFRWT and EGFRT790M: Design, Synthesis, Anticancer Activity and docking simulation

Novel Pyrido-Thiazolo-Pyrimidinone Hybrids targeting EGFRWT and EGFRT790M: Design, Synthesis, Anticancer Activity and docking simulation

Synthesis, Biological Evaluation, and Molecular Docking Studies of Indole‐Based Heterocyclic Scaffolds as Potential Antibacterial Agents

Investigation of bisindole-linked pyrimidine moieties: synthesis using strantium–aluminum supported strontium aluminate nanophosphors catalyst, DNA reactivity, and in silico molecular docking studies

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