Design, synthesis, antiproliferative activity and docking studies of quinazoline derivatives bearing oxazole or imidazole as potential EGFR inhibitors

2018 ◽  
Vol 42 (21) ◽  
pp. 17203-17215 ◽  
Author(s):  
Yiqiang OuYang ◽  
Caolin Wang ◽  
Bingbing Zhao ◽  
Hehua Xiong ◽  
Zhen Xiao ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
Egfr Inhibitors ◽  
Design Synthesis ◽  
Quinazoline Derivatives ◽  
Mcf 7

Six series of quinazoline derivatives bearing oxazole or imidazole (8a–f, 9a–f, 10a–d, 11a–f, 12a–d and 13a–i) were designed, synthesized and their IC50 values evaluated against three cancer cell lines (A549, MCF-7 and PC-3).

scholarly journals Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3041
Author(s):  
Xiaohan Hu ◽  
Sheng Tang ◽  
Feiyi Yang ◽  
Pengwu Zheng ◽  
Shan Xu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Design Synthesis ◽  
Structure Activity ◽  
Excellent Activity ◽  
Ic50 Values ◽  
Mcf 7

Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC50 values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines. The most promising compound, H10, showed not only excellent activity against EGFR kinase but also positive biological activity against PI3K kinase. The structure–activity relationship (SAR) suggested that the introduction of dimethylamine scaffolds with smaller spatial structures was more favorable for antitumor activity. Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents.

scholarly journals Synthesis and Anti-Proliferative Assessment of Triazolo-Thiadiazepine and Triazolo-Thiadiazine Scaffolds

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4471 ◽  
Author(s):  
Ahmed T. A. Boraei ◽  
Hazem A. Ghabbour ◽  
Mohamed S. Gomaa ◽  
El Sayed H. El Ashry ◽  
Assem Barakat
Keyword(s):  
Single Crystal ◽  
Cell Lines ◽  
Cancer Cell ◽  
2D Nmr ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
X Ray ◽  
Cytotoxicity Activity ◽  
Human Liver Cancer ◽  
Mcf 7

A series of triazolo-thiadiazepines 4a–k were synthesized with excellent yields using dehydrated PTSA as a catalyst in toluene. Two triazolo-thiadiazines were obtained; 8a was formed directly by reflux in ethanol, whereas, PTSA promoted the formation of 8b. The molecular structure of the formed triazolo-thiadiazepines is identical to the imine-form 4a–k and not the enamine-tautomer 6a–k. The structures of the newly synthesized triazolo-thiadiazepines 4a–k and triazolo-thiadiazines 8a–b were elucidated using NMR (1H, and 13C), 2D NMR, HRMS, and X-ray single crystal. Furthermore, 4a was deduced using X-ray single crystal diffraction analysis. These new thiadiazepine hits represent an optimized series of previously synthesized indole-triazole derivatives for the inhibition of EGFR. The cytotoxicity activity against two cancer cell lines including human liver cancer (HEPG-2) and breast cancer (MCF-7) was promising, with IC50 between 12.9 to 44.6 µg/mL and 14.7 to 48.7 µg/mL for the tested cancer cell lines respectively, compared to doxorubicin (IC50 4.0 µg/mL). Docking studies revealed that the thiadiazepine scaffold presented a suitable anchor, allowing good interaction of the various binding groups with the enzyme binding regions and sub-pockets.

scholarly journals ANTIPROLIFERATIVE ACTIVITY OF ELEPHANTOPUS SCABER MEDIATED SILVER NANOPARTICLES AGAINST MCF-7, A-549, SCC-40, AND COLO-205 HUMAN CANCER CELL LINES

2019 ◽  
pp. 163-167
Author(s):  
ASHWINI S SHINDE ◽  
VIJAY D MENDHULKAR
Keyword(s):  
Silver Nanoparticles ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Cancer Cell Lines ◽  
Synergistic Activity ◽  
Standard Drug ◽  
Elephantopus Scaber ◽  
The Impact ◽  
Mcf 7

Objective: To unearth the applications of nanotechnology in medicine has become imperative with all the advancements in the technique. In the current study, we have attempted to exploit the anticancer ability of the green synthesized silver nanoparticles (AgNPs). Methods: The AgNPs were synthesized using 60% methanol (H-MeOH) Elephantopus scaber leaf extract, characterized, and discussed priorly. The effect of AgNPs was studied on the human breast (MCF-7), lung (A-549), oral (SCC-40), and colon (COLO-205) cancer cell lines through sulforhodamine B assay. We also carried out the synergistic activity with standard drug adriamycin (ADR). Results: According to the results obtained, AgNPs showed good antiproliferative activity with GI50 <10 μg/ml on MCF-7, A-549, and SCC-40 cell lines when compared with the standard drug ADR. However, for COLO-205 cell line, the impact was 17.4 μg/ml and thus the treatment was less effective. Conclusion: The synergistic effect of AgNPs+ADR was even better for all the four cell lines than that of the AgNPs alone.

Design, Synthesis and Antiproliferative Activity of Novel Phenothiazine-1,2,3-Triazole Analogues

2017 ◽  
Vol 41 (12) ◽  
pp. 696-698 ◽  
Author(s):  
Xiao-Hua Ma ◽  
Nan Liu ◽  
Jing-Li Lu ◽  
Jie Zhao ◽  
Xiao-Jian Zhang
Keyword(s):  
Liver Cancer ◽  
Click Chemistry ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Cancer Cell Lines ◽  
Liver Cancer Cell ◽  
Design Synthesis ◽  
Triazole Derivatives

A series of seven novel 1-aryl-1,2,3-triazole derivatives bearing a 4-(phenothiazin-10-ylmethyl) moiety were designed using a molecular hybridisation approach and synthesised by alkyne/azide click chemistry. Most of the synthesised compounds exhibited moderate to good antiproliferative activity (IC50 values: 0.5 to 6.7 μM) against stomach, oesophagus, prostate, breast and liver cancer cell lines, but a compound containing a 4-chlorophenyl moiety showed better activity against all cell lines than 5-fluorouracil.

scholarly journals New Paracyclophanylthiazoles with Anti-Leukemia Activity: Design, Synthesis, Molecular Docking, and Mechanistic Studies

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3089 ◽  
Author(s):  
Ashraf A Aly ◽  
Stefan Bräse ◽  
Alaa A. Hassan ◽  
Nasr K. Mohamed ◽  
Lamiaa E. Abd El-Haleem ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Annexin V ◽  
Cancer Cell Lines ◽  
Multidrug Resistant ◽  
Docking Studies ◽  
Mechanistic Study ◽  
Design Synthesis ◽  
Apoptotic Activity ◽  
Rpmi 8226

A new series of methyl 2-(2-(4′-[2.2]paracyclophanyl)-hydrazinylidene)-3-substituted-4-oxothiazolidin-5-ylidene)acetates 3a–f were synthesized from the reaction of paracyclophanyl-acylthiosemicarbazides 2a–f with dimethyl acetylenedicarboxylate. Based upon nuclear magnetic resonance (NMR), infrared (IR), and mass spectra (HRMS), the structure of the obtained products was elucidated. X-ray structure analysis was also used as unambiguous tool to elucidate the structure of the products. The target compounds 3a–f were screened against 60 cancer cell lines. They displayed anticancer activity against a leukemia subpanel, namely, RPMI-8226 and SR cell lines. The activity of compound 3a was found as the most cytotoxic potency against 60 cancer cell lines. Consequently, it was selected for further five doses analysis according to National Cancer Institute (NCI) protocol. The cytotoxic effect showed selectivity ratios ranging between 0.63 and 1.28 and between 0.58 and 5.89 at the GI50 and total growth inhibition (TGI) levels, respectively. Accordingly, compound 3a underwent further mechanistic study against the most sensitive leukemia RPMI-8226 and SR cell lines. It showed antiproliferation with IC50 = 1.61 ± 0.04 and 1.11 ± 0.03 µM against RPMI-8226 and SR cell lines, respectively. It also revealed a remarkable tubulin inhibitory activity, compared to colchicine with IC50 = 4.97 µM/mL. Caspase-3, BAX, and Bcl-2 assays for 3a using annexin V-FITC staining revealed significant pro-apoptotic activity. Furthermore, multidrug-resistant leukemia SR cells were used to show better resistance indices (1.285 ng/mL, 1.15-fold) than the reference. Docking studies with β-tubulin indicate that most of the tested compounds illustrated good binding at the colchicine binding site of the enzyme, especially for compound 3a, which made several interactions better than that of the reference colchicine.

scholarly journals Design, Synthesis, and In Vitro Antiproliferative Activity of Hydantoin and Purine Derivatives with the 4-Acetylphenylpiperazinylalkyl Moiety

Materials ◽  
2021 ◽  
Vol 14 (15) ◽  
pp. 4156
Author(s):  
Agnieszka Zagórska ◽  
Anna Czopek ◽  
Anna Jaromin ◽  
Magdalena Mielczarek-Puta ◽  
Marta Struga ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
Chemical Diversity ◽  
Cancer Drug ◽  
Purine Derivatives ◽  
Design Synthesis ◽  
Cancer Drug Discovery

Cancer represents one of the most serious health problems and the second leading cause of death around the world. Heterocycles, due to their prevalence in nature as well as their structural and chemical diversity, play an immensely important role in anti-cancer drug discovery. In this paper, a series of hydantoin and purine derivatives containing a 4-acetylphenylpiperazinylalkyl moiety were designed, synthesized, and biologically evaluated for their anticancer activity on selected cancer cell lines (PC3, SW480, SW620). Compound 4, a derivative of 3′,4′-dihydro-2′H-spiro[imidazolidine-4,1′-naphthalene]-2,5-dione, was the most effective against SW480, SW620, and PC3 cancer cell lines. Moreover, 4 has high tumor-targeting selectivity. Based on docking studies, it was concluded that R isomers of 3′,4′-dihydro-2′H-spiro[imidazolidine-4,1′-naphthalene]-2,5-dione could be further studied as promising scaffolds for the development of thymidine phosphorylase inhibitors.

scholarly journals Antiproliferative, antimicrobial, and antioxidant activity of Lavandula angustifolia Mill. essential oil

2017 ◽  
Vol 7 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Haris Niksic ◽  
Elvira Kovac-Besovic ◽  
Elma Omeragic ◽  
Samija Muratovic ◽  
Jasna Kusturica ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Essential Oil ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Gas Chromatography Mass Spectrometry ◽  
Lavandula Angustifolia ◽  
Mcf 7

Introduction: We studied the chemical composition and antimicrobial, antioxidant, and antiproliferative activities of essential oils from flowers of Lavandula angustifolia grown in Southern Bosnia and Herzegovina. Methods: The chemical profile of essential oil was evaluated by means of gas chromatography-mass spectrometry. Antimicrobial activity was tested against six bacterial strains. The antioxidant activity by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) test and the antiproliferative activity against three human cancer cell lines, MCF-7, NCI-H460, and MOLT-4, were investigated using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide tests. Results: In L. angustifolia essential oil, monoterpene alcohols were the most represented class of volatiles (51.8%), including linalool, lavandulol, and terpinen-4-ol, α-terpineol as the major components, followed by monoterpene esters (22.6%). The most important antibacterial activity of essential oil was expressed on Gram-negative strains. Investigated essential oil was able to reduce DPPH radicals into the neutral DPPH-H form (inhibitory concentration 50% [IC50] = 0.421 mg/ml), and this activity was dose dependent. The essential oil showed significant antiproliferative activity against three cancer cell lines, MOLT-4, MCF-7, and NCI-H460 cells, with IC50 values of 17, 94, and 97 µg/ml, respectively. The result of the antiproliferative assay indicates that MOLT-4 cell line was the most sensitive to investigated essential oil. Conclusion: The results revealed that L. angustifolia essential oil may be important growth inhibitor against the microbes studied. It also possesses significant antioxidant activity and demonstrated excellent antiproliferative activity against MOLT-4 cells.

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