Synthesis of Quinazoline‐1,3,4‐Oxadiazole Linked 1,2,3‐Triazole Hybrids as Potent EGFR Targeting Antilung Cancer Agents: In Vitro, In Silico, and DFT Studies

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(16)

Published: April 1, 2025

Abstract This research focuses on the design and synthesis of novel quinazoline‐1,3,4‐oxadiazole linked 1,2,3‐triazoles. Subsequently, it investigates their in vitro inhibitory effects EGFR kinases anticancer efficacy against lung cancer cell lines A‐549 H1299. Compared to primary compound, erlotinib, most tested compounds demonstrated superior efficacy. The 2‐(((1‐(3,5‐difluorophenyl)‐1 H ‐1,2,3‐triazol‐4‐yl)methyl)sulfonyl)‐5‐(quinazoline‐5‐yl)‐1,3,4‐oxadiazole, 2‐(((1‐(3,5‐dichlorophenyl)‐1 ‐1,2,3‐triazol‐4‐yl)methyl)sulfonyl)‐5‐(quinazolin‐5‐yl)‐1,3,4‐oxadiazole, 2‐(((1‐(4‐fluorophenyl)‐1 ‐1,2,3‐triazol‐4‐yl)methyl)sulfonyl)‐5‐(quinazoline‐5‐yl)‐1,3,4‐oxadiazole showed strong activity both with IC 50 values ranging from 2.62 ± 0.65 4.21 0.24 µM. exhibited notable kinase 0.34 0.03, 0.36 0.04, 0.43 0.02 µM, respectively. In Silico docking experiments were conducted assess molecular interactions more potent drugs human epidermal growth factor receptor, (PDB: 4HJO) proteins, which included a co‐crystallized ligand (erlotinib). results indicated that six active significantly higher binding energies compared standard medications. SWISS/ADME was used estimate pharmacokinetic profile compounds. Geometric optimization also determine structural characteristics compound ‐1,2,3‐triazol‐4‐yl)methyl)sulfonyl)‐5‐(quinazolin‐5‐yl)‐1,3,4‐oxadiazole. electrostatic potential (MEP) HOMO‐LUMO energy gap determined.

Language: Английский

---

Exploring 1,2,3-triazole-Schiff’s base hybrids as innovative EGFR inhibitors for the treatment of breast cancer: In vitro and in silico study

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 155, P. 108106 - 108106

Published: Jan. 4, 2025

Language: Английский

---

One-pot synthesis of fused isoxazolo[4′,5′:4,5]thiopyrano[2,3-d]pyrimidines as potent EGFR targeting anti-lung cancer agents

Tetrahedron Letters, Journal Year: 2024, Volume and Issue: unknown, P. 155325 - 155325

Published: Oct. 1, 2024

Language: Английский

---

Fused Imidazo[1,2‐d][1,2,4]Thiadiazolo[1,2,3]Triazoles: One‐Pot Synthesis, Anti‐Bacterial, Anti‐Biofilm and TLR4 Inhibitory Activities

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(32)

Published: Aug. 23, 2024

Abstract We developed and evaluated several new fused imidazo[1,2‐d][1,2,4]thiadiazolo[1,2,3]triazoles to see how they perform against bacteria biofilms. Some compounds showed acceptable activity compared the primary standard, Dicloxacillin. of demonstrated significant antibacterial S. aureus , with MIC values ranging from 1.56–12.5 μg/mL. also found anti‐biofilm properties in potent compounds. The results that derivatives 3‐(4‐fluorophenyl)imidazo[1,2‐d] [1,2,3] triazolo[1,5‐b][1,2,4]thiadiazole 8,8‐dioxide 3‐(3,5‐difluorophenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole were strong agents effective MSSA MRSA biofilm growth inhibitors. conducted silico studies assess molecular interactions more TLR4 proteins (PDB: 3FXI, 3VQ1, 3RG1). Our findings revealed 3‐(4‐chloro‐3,5‐dimethoxyphenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b] [1,2,4]thiadiazole 8,8‐dioxide, 3‐(3,5‐dichlorophenyl)imidazo[1,2‐d] [1,2,3]triazolo[1,5‐b][1,2,4] 3‐(4‐(trifluoromethyl)phenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b][1,2,4] exhibited binding than dicloxacillin. ADME examined this study could potentially inhibit cytochrome P450 CYP2C19 isoform.

Language: Английский

---

One‐Pot Synthesis of Fused Isoxazolo[4′,5′:3,4]pyrrolo[2,1‐b] Quinazolines as Potent EGFR Targeting Anticancer Agents

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(40)

Published: Oct. 1, 2024

Abstract In response to the need for scaffolds medical applications, synthetic chemists have developed simple and efficient methods optimal synthesis. To investigate synthesis of fused isoxazoles in presence [3+2] cycloaddition followed by C−N bond formation reaction between 3‐((4‐iodo‐3‐phenylisoxazol‐5‐yl)methyl)quinazolin‐4(3H)‐one various nitrile oxides was carried out previously reported conditions. The cancer activities synthesized compounds were then tested vitro against two cell lines, MCF‐7 A‐549. Three compounds, 3‐(3,5‐dichlorophenyl) isoxazolo[4′,5′:3,4]pyrrolo[2,1‐b]quinazolin‐9(11H)‐one, 3‐(4‐fluorophenyl)isoxazolo[4′,5′:3,4]pyrrolo[2,1‐b]quinazolin‐9(11H)‐one, 3‐(4‐(trifluoromethyl)phenyl)isoxazolo[4′,5′:3,4] pyrrolo[2,1‐b] quinazolin‐9(11H)‐one has shown superior activity non‐small‐cell lung line (A‐549) than standards 5‐fluorouracil erlotinib. Later, EGFR results revealed that a more potent compound effective conventional medicine, silico investigations erlotinib on protein indicated had comparable binding energies inhibition constants

Language: Английский

---

Utilizing perhalopyridine-based alkynes as suitable precursors for the synthesis of novel poly(1,2,3-triazolyl)-substituted perhalopyridines

RSC Advances, Journal Year: 2024, Volume and Issue: 14(42), P. 30873 - 30885

Published: Jan. 1, 2024

A novel series of poly(1,2,3-triazolyl)-substituted perhalopyridines were synthesized under ultrasonic irradiation. We also developed an effective method for the preparation ((1,2,3-triazol-4-yl)methoxy)-3,4,5,6-tetrachloropyridines.

Language: Английский

---

Synthesis of New Imidazolo‐Benzenesulfonamide Linked 1,2,3‐Triazoles as Potent Antibacterial and Antibiofilm Agents

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(38)

Published: Oct. 1, 2024

Abstract In search of better antibacterial and antibiofilm agents, this report presents a series novel 1,2,3‐triazole‐imidazole‐benzenesulfonamide derivatives that were synthesized evaluated for their activity in vitro. Antibacterial against three Gram‐positive bacterial strains, B. subtilis , S. aureus epidermidis was evaluated. Among all the tested compounds, 4‐methyl‐ N ‐(1‐methyl‐1 H ‐imidazol‐2‐yl)‐ ‐((1‐(4‐(trifluoromethyl)phenyl)‐1 ‐1,2,3‐triazol‐4‐yl)methyl)benzenesulfonamide ‐((1‐(3,5‐difluorophenyl)‐1 ‐1,2,3‐triazol‐4‐yl)methyl)‐4‐methyl‐ ‐imidazol‐2‐yl)benzenesulfonamide exhibited potent strains. Biofilm profiles compounds it observed from results above two active displayed promising biofilm inhibition with MIC values ranging between 2.19 ± 0.37 3.38 0.35 µg/mL. Furthermore, screened silico molecular docking studies penicillin‐binding protein compound ‐((1‐(3,5‐dichlorophenyl)‐1 show highest binding energy as compared to standard remaining compounds.

Language: Английский

---