Synthesis and Biological Evaluation of Novel 1,2,3-Triazole Based Pyrido[4,3-d]pyrimidines as Potent Anticancer and EGFR Inhibitors

Sreerama, Rakesh; Kumar, Nitin; Nukala, Satheesh Kumar; Sucharitha, E. Ramya; Babu, H. Ramesh; Narsimha, Sirassu

doi:10.1134/s1070363221120227

Cited by 13 publications

(3 citation statements)

References 18 publications

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“…The synthesis of the title compounds is as outlined in Scheme [1,4]thiazine 1,1-dioxide (4). 32 The 1,3-dipolar cycloaddition of terminal alkyne 4 with various aryl azides (5a-5j) using a catalytic amount of copper iodide at room temperature provided the corresponding 1,2,3triazole-piperazin-benzo[b] [1,4]thiazine 1,1-dioxide (6a-6j) in good to excellent yields. 33 Similarly, the alkyne 4 with different aryl sulfonyl azides (7a-7g) using catalytic amount of copper iodide at 60 °C temperature for 10-12 h to form corresponding sulfonyl 1,2,3-triazole-piperazin-benzo[b] [1,4]thiazine 1,1dioxide (8a-8g) in good to excellent yields (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of 1,2,3-triazole-piperazin-benzo[b][1,4]thiazine 1,1-dioxides: antibacterial, hemolytic and in silico TLR4 protein inhibitory activities

Ramu,

Krishna,

Kapavarapu

et al. 2024

RSC Adv.

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Section: Resultsmentioning

confidence: 99%

“…Compounds 3 further reacted with 1-(prop-2-yn-1-yl)piperazine in dioxane in presence of triethyl amine to obtain key intermediate 3-(4-(prop-2-yn-1-yl)piperazin-1-yl)-2 H -benzo[ b ][1,4]thiazine 1,1-dioxide (4). 32 …”

Section: Resultsmentioning

confidence: 99%

Synthesis of 1,2,3-triazole-piperazin-benzo[b][1,4]thiazine 1,1-dioxides: antibacterial, hemolytic and in silico TLR4 protein inhibitory activities

Ramu,

Krishna,

Kapavarapu

et al. 2024

RSC Adv.

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“…Molecular docking studies were carried out using Auto dock tools by taking epidermal growth factor receptor (EGFR) as the target because there are many number of reports related to EGFR inhibition by quinoline, morpholine and 1,2,3‐triazole based hybrid molecules [19a–l] . The protein was downloaded in pdb format (pdb id‐4HJO) from protein data bank [20] .…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

Synthesis of Quinoline‐Morpholine‐Coupled 1,2,3‐Triazole Hybrids as In vitro EGFR inhibitors

Mamidala

Bokkala²,

Thirukovela³

et al. 2022

ChemistrySelect

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Herein we described the synthesis of some new quinolinemorpholine coupled 1,2,3-triazole hybrids (6 a-n) from 5chloroquinolin-8-ol using well known reactions like Mannich reaction, O-propargylation, and finally copper (I) catalyzed azide-alkyne cycloaddition (CuAAC). The structures of all newly synthesized hybrids were confirmed by 1 H-NMR, 13 C-NMR, and Mass spectra. All of them were screened for their in vitro cytotoxicity towards three human cancer cell lines including MCF-7, A549 and HepG2 by MTT assay where four compounds (6 c, 6 j, 6 m and 6 n) exhibited more potency than the reference erlotinib against all the three cell lines. In vitro tyrosine kinase EGFR inhibition assay for the same four compounds revealed that 6 m has triple inhibiting power with IC 50 value of 0.14 μM and 6 j has nearly double inhibiting power with IC 50 value of 0.22 μM compared to erlotinib. Molecular docking studies with EGFR have shown that all the above four compounds have more binding energies (À 9.09 kcal/mol to À 9.96 kcal/mol) than that of erlotinib (-7.69 kcal/mol). Finally, in silico pharmacokinetic profile was achieved using SWISS/ADME and pkCSM, where all the four compounds followed Lipinski rule, Veber rule, Egan rule and Muegge rule and the lipophilicity (ClogP) was found to be ranging from 2.98 to 3.69.

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Cu(I)‐Catalyzed One‐Pot Synthesis of [1,2,3]Triazolo[5,1‐a] isoquinolin‐6(5H)‐one Derivatives as EGFR‐Targeting Anticancer Agents

Samala¹,

Nukala²,

Thirukovela³

et al. 2022

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The CuI promoted one‐pot multi‐component synthesis of new fused [1,2,3]triazolo[5,1‐a]isoquinoline derivatives (4 a–4 h, 8 a–8 f & 9 a–9 f) without isolating unsafe azides and their in vitro cytotoxic activity against MCF‐7 & MDA‐MB‐231 (breast cancer cells) and A‐549 (alveolar carcinoma) was reported herein. Out of all, compounds 9‐chloro‐1‐(morpholinomethyl)‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (8 d), 9‐fluoro‐1‐(morpholinomethyl)‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (8 e), 9‐chloro‐1‐((1,1‐dioxidothiomorpholino)methyl)‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (9 d), and 1‐((1,1‐dioxidothiomorpholino)methyl)‐9‐fluoro‐[1,2,3]triazolo[5,1‐a]isoquinolin‐6(5H)‐one (9 e) showed superior potency against all the cell lines than the standard drug erlotinib with IC50 values ranging from 2.45 to 7.19 μM. The most active compounds 8 d, 8 e, 9 d, and 9 e were also screened for their efficacy in inhibiting tyrosine kinase EGFR and results revealed that compound 9 d showed comparable activity with standard drug erlotinib, whereas, compounds 8 d, 8 e, and 9 e showed superior activity than the erlotinib. Molecular modeling studies for active compounds on EGFR (PDB‐ID‐4HJO) were also conducted and the obtained free energies were observed to be in agreement with the in vitro activity data. Finally, compounds 8 d, 8 e, 9 d, and 9 e didn't show AMES toxicity and followed the rules of Egan, Ghose, Veber, Lipinski, and Muegge rules without any deviation.

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Synthesis and Biological Evaluation of Novel 1,2,3-Triazole Based Pyrido[4,3-d]pyrimidines as Potent Anticancer and EGFR Inhibitors

Cited by 13 publications

References 18 publications

Synthesis of 1,2,3-triazole-piperazin-benzo[b][1,4]thiazine 1,1-dioxides: antibacterial, hemolytic and in silico TLR4 protein inhibitory activities

Synthesis of 1,2,3-triazole-piperazin-benzo[b][1,4]thiazine 1,1-dioxides: antibacterial, hemolytic and in silico TLR4 protein inhibitory activities

Synthesis of Quinoline‐Morpholine‐Coupled 1,2,3‐Triazole Hybrids as In vitro EGFR inhibitors

Cu(I)‐Catalyzed One‐Pot Synthesis of [1,2,3]Triazolo[5,1‐a] isoquinolin‐6(5H)‐one Derivatives as EGFR‐Targeting Anticancer Agents

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