EGFR, HER2 target based molecular docking analysis, in vitro screening of 2, 4, 5-trisubstituted imidazole derivatives as potential anti-oxidant and cytotoxic agents (original) (raw)
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POLYCYCLIC AROMATIC COMPOUNDS, 2024
Herein, we prepared some new imidazole-1,2,4-oxadiazole hybrids (6a-6o) and investigated their antiproliferative potential on three human cancer cell lines (HepG2, A549 and MCF-7) using Erlotinib as standard drug. In common, most of the compounds showed better potential on MCF-7 in comparison to HepG2 and A549. Out of all, compound 6o had greater activity on MCF-7, while, it, had most promising activity on HEPG2 and A549. Compounds 6f, 6j and 6l also exhibited significant activity on MCF-7. As well, in vitro anti-EGFR evaluation of most active compounds 6f, 6j, 6l, and 6o revealed that compound 6o displayed most promising activity as compared to Erlotinib. Molecular docking studies revealed the possible binding interactions of derivatives 6f, 6j, 6l, and 6o with EGFR (PDB ID-4HJO). Finally, compounds 6f, 6j, 6l, and 6o are possessing 'druglikeness' with CLogP values ranging from 1.86 to 3.13.
2015
Objectives: The objective of this work is to synthesize novel imidazole and fused imidazole derivatives using 5-arylidene-2-hydrazino-3-phenyl imidazolin-4-ones (5a-c) as key intermediate. The structure of the newly synthesized compounds was characterized using IR, 1HNMR, Mass spectroscopy, elemental analysis and some representative 13 Methods: The target compounds were synthesized starting from 5-arylidene-2-hydrazino-3-phenyl imidazolin-4-ones (5a-c) which prepared from the appropriate 5-arylidene-2-(methylthio)-3-phenyl imidazolin-4-ones (3a-c). Several synthetic pathways were be used for the preparation of the targets. Some of the newly synthesized compounds were evaluated for their cytotoxic activity against breast carcinoma and colon carcinoma cell lines. On the other hand, the antimicrobial activity evaluation of some newly prepared compounds was performed using cup plate diffusion method. CNMR.
“SYNTHESIS, INSILICO STUDY & ANTI-PROLIFERATIVE ACTIVITY OF NEW DERIVATIVES OF TRI-ARYL IMIDAZOLE”
2022
This study focuses on the process of Docking, Synthesis, and Characterization of novel chemotherapeutic agents with the potential Anticancer Activity. The aim is to discover new compounds for the anticancer activity using MCF7 cell lines on Breast Cancer that exhibit promising properties for Cancer Treatment. Imidazole offers better pharmacodynamic characteristics and directly affect membranes at high concentrations, independent of sterols and sterol esters. Recent developments in imidazole derivatives for drug development show improved efficacy & lower toxicity. The docking approach to assess the binding affinity and interaction between compounds & Protein. Radziszewski synthesis scheme with substituted benzyls and quinoline aldehyde employed to create imidazole compounds. The synthesized Compounds are subsequently analyzed using various techniques like NMR (1H), TLC, FT-IR, Mass Spectral data, Biological evaluation to assess their ability to inhibit cancer cell growth or induce cancer cell death. The findings obtained from this study seek to make a valuable contribution to the advancement of novel chemotherapeutic agents with improved anticancer properties.
Docking, Synthesis and Evaluation of Antioxidant Activity of 2,4,5-Triaryl Imidazole
Clinical & Medical Biochemistry: Open Access, 2015
A series of nitrogen-containing heterocyclic compounds such as substituted 2,4,5-triaryl imidazole were synthesized by benzyl, ammonium acetate and aromatic/heteroaromatic aldehyde, evaluated for their antioxidant activity by DPPH method. Among the screened compounds, electron rich imidazole exhibited significant antioxidant activities.
Bulletin of the Chemical Society of Ethiopia, 2020
Carbazoles and imidazole represent two important classes of heterocycles which exhibit diverse biological activities such as antitumor properties. In this study, imidazole (C1-C3) and carbazole (C4 and C5) derivatives were evaluated for their cytotoxic activity against three human cancer cell lines namely, MCF7 (human breast cancer), HT29 (human colon cancer), and HeLa (human cervical cancer). Carbazole derivatives (C4 and C5) with IC50 < 10 µM showed greater cytotoxic effect than imidazole derivatives (C1-C3). Furthermore, all compounds exhibited better anticancer activity against MCF-7 than other two cell lines (HT-29, HeLa) and compound C4 was the most potent compound with the IC50 values of 2.5, 5.4 and 4.0 µM, against MCF-7, Hela and HT-29 cell lines, respectively. Physicochemical properties of compounds were calculated and their correlation with the IC50 values on MCF-7 cell line investigated. Surface area and polarizability of compounds showed good correlation by R2 = 0.83...
European journal of medicinal chemistry, 2017
The synthesis of benzimidazole linked oxadiazole derivatives designed as potential EGFR and erbB2 receptor inhibitors with anticancer and apoptotic activity were studied. Compounds 7a specifically inhibit EGFR and erbB2 receptor at 0.081 and 0.098 μM concentration. Some of the compounds showed strong, broad-spectrum antiproliferative activitiy when tested against five human cancer cell lines. Compounds 7a and 7n were more cytotoxic than 5-fluorouracil against MCF-7 cancer cell, with IC50 values of 5.0 and 2.55 μM whereas, only 7a led to cell cycle arrest at G2/M phase accompanied by an increase in apoptosis. Compounds 7a and 7n showed normal architecture of myofibrils in cardiomyopathy study whereas only compound 7a showed nearly equal biochemical parameters (SGOT and SGPT) when compared to control. Molecular docking & 3D-QSAR studies were used to establish interactions of 7a and 7n within the active site of enzyme for ATP binding site of kinase domain.
Applied Sciences, 2020
The employment of privileged scaffolds in medicinal chemistry supplies scientists with a solid start in the search for new and improved therapeutic molecules. One of these scaffolds is the imidazole ring, from which several derivatives have shown a wide array of biological activities. A series of 2,4,5-triphenyl imidazole derivatives were synthesized, characterized, and evaluated in vitro as antioxidant molecules using 1,1-diphenyl-2-picrylhydrazyl (DPPH.) and 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS.+) assays, acetylcholinesterase (AChE) and xanthine oxidase (XO) inhibitors as well as antiproliferative agents. Additional in silico studies such as docking and determination of their absorption, distribution, metabolism, and excretion (ADME) properties were calculated. Compounds 3 and 10 were the most active antioxidants in both the DPPH and ABTS assays (EC50 of 0.141 and 0.174 mg/mL, and 0.168 and 0.162 mg/mL, respectively). In the enzymatic inhibition, compound 1 sh...
2020
In the present study of 4,5-diphenyl-1-((tetrahydrofuran-2-yl)methyl)-2-(3,4,5-trichlorophenyl)1H-imidazole 1 was synthesized. The synthesized imidazole compound 1 has been characterized by FTIR, H, C NMR and ESI-Mass spectral studies. Molecular docking is also performed in order to explain the over-expression of estrogen receptor in 70% of liver cancer. The imidazole scaffold is a privileged scaffold for exploration of anticancer agents. The objective of the present study is to evaluate the anticancer activity of imidazole 1 in human liver cancer cell lines HepG2.
In present investigation; we tried to authenticate quinazoline derivatives, which are extensively reported in the literature as antiulcer agent. In doing so we attempted virtual ligand screening; which found more promising as compare to high throughput screening in overcoming the limitations of unprecedented number of novel leads. We selected fifty one novel 2-[5-substituted-1-H benzo(d)imidazole-2-yl sulfinyl]methyl-3-substituted quinazoline-4(3H)one and subsequently docked them into newly generated homology model of H + /K + ATPase at BioMed CAChe workstation V6.1.1.The analogues 42 and 43 were found promising. Omeprazole is selected as a standard. Structure based drug designing of these analogues may found a novel antiulcer drug at future study.
Synthesis and biological evaluation of imidazol-2-one derivatives as potential antitumor agents
Bioorganic & Medicinal Chemistry, 2008
Two positional isomers with the general formula 1H-imidazol-1-ylmethylacridin-9(10H)-one were synthesized (5, 6) and evaluated for their inhibitory activity versus CYP11B1, CYP11B2, CYP17 and CYP19. Compound 5 was more effective than letrozole in inhibiting CYP19 (aromatase). Interestingly, compound 5 also inhibited CYP11B1 with an IC 50 of 21.2 nM. On the other hand compound 6 was almost completely inactive against all CYPs; this indicates that the positioning and spatial orientation of the imidazolylmethyl moiety is of paramount importance to activity. Sequence alignment of the four steroidogenic CYP enzymes and docking studies with 5, 6 and letrozole supported this finding and suggested Ser478 to be an essential residue for both inhibition and selectivity. These novel compounds may have benefits for the treatment of Cushing's syndrome, hypertension, congestive heart failure and myocardial fibrosis and breast cancer.