scholarly journals Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

2020 ◽  
Vol 13 (11) ◽  
pp. 393
Author(s):  
Tarek S. Ibrahim ◽  
Mohamed M. Hawwas ◽  
Azizah M. Malebari ◽  
Ehab S. Taher ◽  
Abdelsattar M. Omar ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tubulin Polymerization ◽  
Design Synthesis ◽  
Cycle Arrest ◽  
M Phase ◽  
Ic50 Values ◽  
Low Cytotoxicity ◽  
Induced Apoptosis ◽  
Derivatives Of ◽  
Mcf 7

A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most potent compound, 19h, demonstrated superior IC50 values ranging from 0.02 to 0.04 µM against four cancer cell lines while maintaining low cytotoxicity in MCF-10A non-cancer cells, thereby suggesting 19h’s selectivity towards proliferating cancer cells. In addition to tubulin polymerization inhibition, 19h caused cell cycle arrest in MCF-7 cells at the G2/M phase and induced apoptosis. Collectively, these findings indicate that 19h holds potential for further investigation as a potent chemotherapeutic agent targeting tubulin.

Hybridized Quinoline Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and Molecular Docking

2019 ◽  
Vol 19 (4) ◽  
pp. 439-452 ◽  
Author(s):  
Mohamed R. Selim ◽  
Medhat A. Zahran ◽  
Amany Belal ◽  
Moustafa S. Abusaif ◽  
Said A. Shedid ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Caspase 3 ◽  
Biological Evaluation ◽  
Tubulin Polymerization ◽  
Design Synthesis ◽  
Chemical Structures ◽  
M Phase ◽  
Induced Apoptosis ◽  
Derivatives Of

Objective: Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer active agents. Methods: Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline 7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin polymerization inhibition and cell cycle analysis were evaluated. Results: Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds 3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis. Conclusion: Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation and optimization.

Design, synthesis of novel quinazolinone-based oxobutanonitrile derivatives as antiproliferative agents targeting human breast cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Omaima Mohamed AboulWafa ◽  
Hoda Mohamed Gamal El-Din Daabees ◽  
Eman Salah Ezz-ElDien
Keyword(s):  
Breast Cancer ◽  
Binding Affinities ◽  
Caspase 9 ◽  
Design Synthesis ◽  
Egfr Inhibition ◽  
Cycle Arrest ◽  
M Phase ◽  
Quinazolinone Derivatives ◽  
Mcf 7

Background: Breast cancer (BC) is among the leading causes of death among women worldwide. Medical interest has focused on quinazolinone derivatives approved and utilized in antitumor medications. Objective: Novel quinazolinone-based oxobutanonitrile derivatives were designed, synthesized, and screened for in vitro anti-BC activity. Methods: The antiproliferative activities were determined using MTT assay against MCF-7 and MDA-MB-231 cell lines. EGFR, ARO, and caspase-9 enzymes were selected to explore the mechanism of action of the most potent compounds. Results: Tested compounds showed better EGFRIs than ARIs. In addition, significant overexpression in caspase-9 level in treated MCF-7 breast cell line samples was observed with the most active compounds. The thienyl derivative 5 induced the greatest activation in caspase-9 level in treated MCF-7 breast cancer samples. The o-tolylhydrazone 3b, exhibiting promising ARO inhibition and weak EGFR inhibition, produced a noticeable high overexpression of caspase-9 and showed pre-G1 apoptosis and cell cycle arrest at G2/M phase for MCF-7 cells and at S-phase for MDA-MB-231 cells. Docking results revealed that 3b, elicited binding affinities to ARO comparable to those of letrozole. Conclusion: The obtained results support the therapeutic importance of some of these compounds as anti-BC agents in light of the simple methodology used for their synthesis. Their design offered a way for the optimization and development of apoptotic quinazolinone-based ARO and EGFR inhibitors.

scholarly journals A Flavone Constituent from Myoporum bontioides Induces M-Phase Cell Cycle Arrest of MCF-7 Breast Cancer Cells

Molecules ◽  
2017 ◽  
Vol 22 (3) ◽  
pp. 472 ◽  
Author(s):  
Jing-Ru Weng ◽  
Li-Yuan Bai ◽  
Wei-Yu Lin ◽  
Chang-Fang Chiu ◽  
Yu-Chang Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Phase Cell ◽  
Cycle Arrest ◽  
M Phase ◽  
Mcf 7

scholarly journals Synthesis and Evaluation of Triazolyl Dihydropyrimidines as Potential Anticancer Agents

2018 ◽  
Vol 10 (4) ◽  
pp. 18
Author(s):  
Rajanna Ajumeera ◽  
Ganapathi Thipparapu ◽  
Shireesha Boyapati ◽  
Bharath Singh Padya ◽  
Vijayalaxmi Venkatesan
Keyword(s):  
Anticancer Agents ◽  
Human Breast Cancer Cell ◽  
S Phase ◽  
Human Breast ◽  
Standard Drug ◽  
M Phase ◽  
Ic50 Values ◽  
Derivatives Of ◽  
Mcf 7

Novel N – triazolyl 3(a-f) and O-triazolyl (4a-f) derivatives of 4, 6-diaryl-1, 4-dihydropyrimidines were synthesized through mannich reaction. All compounds were characterized by physical and spectral data. These compounds were screened for in vitro efficiency in human breast cancer cell (MCF-7&MDA-MB-231) lines and found to have very good anti-proliferative activity.  Among all compounds of 4b, 3e, 4e endowed with lesser respective IC50 values of 31.94, 55.73, 55.03 µM in MCF-7 cells and 41.50, 35.28, 32.06 µM in MDA-MB 231 cells by MTT assay. In further studies, Compounds 4b, 3e, 4e were found to arrest cell growth at S phase in MCF-7 cells. In MDA-MB 231 cells, 4b, 4e were found to arrest the cells in S phase, and compound 3e found to arrest G2/M phase when compared to the standard drug tamoxifen, arrested S phase in MCF-7 cells and G0/G1 phase in MDA-MB 231 cells.

scholarly journals Marine-Inspired Bis-indoles Possessing Antiproliferative Activity against Breast Cancer; Design, Synthesis, and Biological Evaluation

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 190 ◽  
Author(s):  
Wagdy M. Eldehna ◽  
Ghada S. Hassan ◽  
Sara T. Al-Rashood ◽  
Hamad M. Alkahtani ◽  
Abdulrahman A. Almehizia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Annexin V ◽  
Fold Increase ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Lead Compounds ◽  
M Phase ◽  
Indole Series ◽  
Induced Apoptosis ◽  
Mcf 7

Diverse indoles and bis-indoles extracted from marine sources have been identified as promising anticancer leads. Herein, we designed and synthesized novel bis-indole series 7a–f and 9a–h as Topsentin and Nortopsentin analogs. Our design is based on replacing the heterocyclic spacer in the natural leads by a more flexible hydrazide linker while sparing the two peripheral indole rings. All the synthesized bis-indoles were examined for their antiproliferative action against human breast cancer (MCF-7 and MDA-MB-231) cell lines. The most potent congeners 7e and 9a against MCF-7 cells (IC50 = 0.44 ± 0.01 and 1.28 ± 0.04 μM, respectively) induced apoptosis in MCF-7 cells (23.7-, and 16.8-fold increase in the total apoptosis percentage) as evident by the externalization of plasma membrane phosphatidylserine detected by Annexin V-FITC/PI assay. This evidence was supported by the Bax/Bcl-2 ratio augmentation (18.65- and 11.1-fold compared to control) with a concomitant increase in the level of caspase-3 (11.7- and 9.5-fold) and p53 (15.4- and 11.75-fold). Both compounds arrested the cell cycle mainly in the G2/M phase. Furthermore, 7e and 9a displayed good selectivity toward tumor cells (S.I. = 38.7 and 18.3), upon testing of their cytotoxicity toward non-tumorigenic breast MCF-10A cells. Finally, compounds 7a, 7b, 7d, 7e, and 9a were examined for their plausible CDK2 inhibitory action. The obtained results (% inhibition range: 16%–58%) unveiled incompetence of the target bis-indoles to inhibit CDK2 significantly. Collectively, these results suggested that herein reported bis-indoles are good lead compounds for further optimization and development as potential efficient anti-breast cancer drugs.

Novel phenyl and thiophene dispiro indenoquinoxaline pyrrolidine quinolones induced apoptosis via G1/S and G2/M phase cell cycle arrest in MCF-7 cells

2020 ◽  
Vol 44 (35) ◽  
pp. 15031-15045
Author(s):  
Selvaraj Shyamsivappan ◽  
Arjunan Saravanan ◽  
Raju Vivek ◽  
Thangaraj Suresh ◽  
Ramasamy Shankar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cycloaddition Reaction ◽  
Phase Cell ◽  
One Pot ◽  
Cycle Arrest ◽  
M Phase ◽  
Induced Apoptosis ◽  
Mcf 7

New phenyl and thiophene dispiro indeno quinoxaline pyrrolidine quinolone analogues were synthesized by a one-pot four-component [3+2] cycloaddition reaction between (E)-3-arylidene-2,3-dihydro-8-nitro-4-quinolones, o-phenylenediamine, ninhydrin, and benzylamine/thiophenemethylamine.

scholarly journals The Parotoid Gland Secretion from Peruvian Toad Rhinella horribilis (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer Cells

Toxins ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 608
Author(s):  
Guillermo Schmeda-Hirschmann ◽  
Jean Paulo de Andrade ◽  
Marilú Roxana Soto-Vasquez ◽  
Paul Alan Arkin Alvarado-García ◽  
Charlotte Palominos ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Cancer Cells ◽  
Biological Effects ◽  
A549 Cells ◽  
Bioactive Substances ◽  
M Phase ◽  
Ic50 Values ◽  
And Migration ◽  
Induced Apoptosis ◽  
Proliferation And Migration

Since Rhinella sp. toads produce bioactive substances, some species have been used in traditional medicine and magical practices by ancient cultures in Peru. During several decades, the Rhinella horribilis toad was confused with the invasive toad Rhinella marina, a species documented with extensive toxinological studies. In contrast, the chemical composition and biological effects of the parotoid gland secretions (PGS) remain still unknown for R. horribilis. In this work, we determine for the first time 55 compounds from the PGS of R. horribilis, which were identified using HPLC-MS/MS. The crude extract inhibited the proliferation of A549 cancer cells with IC50 values of 0.031 ± 0.007 and 0.015 ± 0.001 µg/mL at 24 and 48 h of exposure, respectively. Moreover, it inhibited the clonogenic capacity, increased ROS levels, and prevented the etoposide-induced apoptosis, suggesting that the effect of R. horribilis poison secretion was by cell cycle blocking before of G2/M-phase checkpoint. Fraction B was the most active and strongly inhibited cancer cell migration. Our results indicate that the PGS of R. horribilis are composed of alkaloids, bufadienolides, and argininyl diacids derivatives, inhibiting the proliferation and migration of A549 cells.

Cyclization of flavokawain B reduces its activity against human colon cancer cells

2019 ◽  
Vol 39 (3) ◽  
pp. 262-275 ◽  
Author(s):  
A Palko-Łabuz ◽  
E Kostrzewa-Susłow ◽  
T Janeczko ◽  
K Środa-Pomianek ◽  
A Poła ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Structural Parameters ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Cycle Arrest ◽  
Biological Studies ◽  
M Phase ◽  
Induced Apoptosis

Chalcones are naturally occurring compounds exhibiting biological activity through multiple mechanisms. Flavokawain B is one of chalcones found in kava plant. In our studies, we focused on the anticancer activity of flavokawain B in colorectal cancer cells LoVo and its resistant to doxorubicin subline—LoVo/Dx. Strong cytotoxic activity of flavokawain B and its ability to inhibit the proliferation in both cell lines was detected. These effects accompanied with induction cell cycle arrest in G2/M phase and the presence of SubG1 fraction. Flavokawain B at low concentration led to increase of caspase-3 activity. The chalcone-induced apoptosis was also confirmed by DNA fragmentation. In our work, the conversion of flavokawain B to corresponding flavanone—5,7-dimetoxyflavanone—was shown to be more extensive in cancer than in non-cancer cells. We found that the cyclization of the chalcone was related to the significant decrease in the cytotoxicity. Cell proliferation and cell cycle progression were not impaired significantly in the studied cancer cells incubated with 5,7-dimethoxyflavanone. We did not observe apoptosis in the cells incubated with flavanone. The results from biological studies agreed with the theoretical activity that emerges from structural parameters.

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