Synthesis, biological evaluation and molecular docking of new triphenylamine-linked pyridine, thiazole and pyrazole analogues as anticancer agents

Abstract

A new series of pyridine, thiazole, and pyrazole analogues were synthesized. The pyridone analogues 4a-e were synthesized by treating N-aryl-2-cyano-3-(4-(diphenylamino)phenyl)acrylamides 3a-e with malononitrile. Many 4-arylidene-thiazolidin-5-one analogues 6a-d were obtained by Knoevenagel reactions of 4-(diphenylamino)benzaldehyde (1) with their corresponding thiazolidin-5-one derivatives 5a-d. The structural elucidation of the products was proven by the collections of spectroscopic methods such as IR, 1H NMR, 13C NMR, and MS data. Their anti-cancer activity was examined against two cell lines, MDA-MB-231 (mammary carcinomas) and A-549 (lung cancer). Compared with cisplatin as a reference standard drug, 6-amino-4-(4-(diphenylamino)phenyl)-2-oxo-1-(p-tolyl)-1,2-dihydropyridine-3,5-dicarbonitrile (4b) and 6-amino-4-(4-(diphenylamino)phenyl)-1-(4-nitrophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (4e) exhibited better efficiency against the A-549 cell line, with IC50 = 0.00803 and 0.0095 μM, respectively. Also, these compounds 4b and 4e showed the most potency among the examined compounds against MDA-MB-231 with IC50 = 0.0103 and 0.0147 μM, respectively. The newly synthesized compounds were docked inside the active sites of the selected proteins and were found to demonstrate proper binding. 2-Cyano-2-(4,4-(diphenylamino)benzylidene)-5-oxo-3-phenylthiazolidin-2-ylidene)-N-(p-tolyl)acetamide (6c) offered the highest binding affinity (− 8.1868 kcal/mol) when docked into (PDB ID:2ITO), in addition to 2-cyano-N-(4-(diethylamino)phenyl)-2-(4-(4-(diphenylamino)benzylidene)-5-oxo-3-phenylthiazolidin-2-ylidene)acetamide (6a) gave the highest energy score (− 9.3507 kcal/mol) with (PDB ID:2A4L).

Synthesis, Biological Evaluation, and Docking Study of a New Series of Thiophene Derivatives Based on 3‐Oxobutanamidothiophene as an Anticancer Agent

“…The cancer cells were cultured in a 96‐well plate at a volume of (100 L/well), following the methods of Skehan et al . with slight modifications [31,32] . Initially, the cells were exposed to DMSO (0.5 % V/V) or 50 M of each tested chemical for an overnight incubation at 37 °C and 5 % CO2.…”

“…The cancer cells were cultured in a 96-well plate at a volume of (100 L/well), following the methods of Skehan et al with slight modifications. [31,32] Initially, the cells were exposed to DMSO (0.5 % V/V) or 50 M of each tested chemical for an overnight incubation at 37 °C and 5 % CO2. After 48 h, MTT reagent (5 mg/mL in Phosphate Buffered Saline (PBS)) was added to the plate and incubated for an additional 4 h. Subsequently, formazan crystals were dissolved using a solution of acidified sodium dodecyl sulphate (SDS) (10 % SDS with 0.01 N HCl in 1× PBS).…”

“…The IC50 value was determined by treating the cells with various concentrations (1.56, 3.125, 6.25, 12.5, 25, and 50 μM) of the most potent compounds, and cell viability was evaluated as described earlier. [31,32] Supporting Information Summary IR, 1 H-NMR and Mass spectra of new thiophene compounds are included in the Supporting Information file and images of Molecular docking.…”

A promising perspective through potential antimicrobial, anti‐cancer, and antiviral activity against SARS‐CoV‐2 of silver(I) complexes: Synthesis, characterization, density functional theory calculations, and in‐silico molecular docking studies

“…61 Likewise, breast cancer is a grave disease comprising heterogeneous tumors allied with a characteristic histological pattern and diverse clinical features. 62 In this context, the tested silver complexes are arranged and compared with the vinblastine drug in the following order: vinblastine > 3 > HGMF > 1 > 2. Interestingly, the displayed higher cytotoxicity of complex 3 via the examined cell lines may be due to its higher DNA binding affinity than the other prepared silver complexes.…”

A comprehensive analysis of the role of molecular docking in the development of anticancer agents against the cell cycle CDK enzyme

“…Many groups have worked on CDK2 inhibition with the help of molecular docking. For instance, (Mansour et al, 2021b, Elmorsy et al, 2022 reported novel pyridine-3carbonitrile derivatives as anticancer compounds against the CDK2 enzyme (79-82) (Fig. 19), Eldehna and his group studied three series of oxindole-benzofuran hybrids (83-85) (Eldehna et al, 2021a) (Fig.…”