scholarly journals Multi-component Reactions of Cyclohexan-1,3-diketones to Produce Fused Pyran Derivatives with Antiproliferative Activities and Tyrosine Kinases and Pim-1 Kinase Inhibitions

2021 ◽  
Vol 68 (1) ◽  
pp. 51-64
Author(s):  
Rafat Milad Mohareb ◽  
Rehab Ali Ibrahim ◽  
Ensaf Sultan Alwan
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Tyrosine Kinases ◽  
Ethyl Cyanoacetate ◽  
Cancer Cell Lines ◽  
The Other ◽  
Thiazole Derivatives ◽  
Dione Derivative ◽  
Cytotoxic Compounds ◽  
Antiproliferative Activities

In this work the multi-component reactions of either of the arylhydrazocyclohexan-1,3-dione derivatives 3a–c with either of benzaldehyde (4a), 4-chlorobenzaldehyde (4b) or 4-methoxybenzaldehyde (4c) and either malononitrile (5a) or ethyl cyanoacetate (5b) giving the 5,6,7,8-tetrahydro-4H-chromene derivatives 6a–r, respectively, are presented. The reaction of two equivalents of cyclohexan-1,3-dione with benzaldehyde gave the hexahydro-1H-xanthene-1,8(2H)-dione derivative 7. On the other hand, the multi-component reactions of compound 1 with dimedone and benzaldehyde gave 13. Both of 7 and 13 underwent heterocyclization reactions to produce fused thiophene, pyran and thiazole derivatives. Selected compounds among the synthesized compounds were tested against six cancer cell lines where most of them gave high inhibitions; especially compounds 3b, 3c, 6b, 6c, 6d, 6f, 6i, 6m, 6n, 8b, 14a, 15 and 16 being the most cytotoxic compounds. Further tests against the five tyrosine kinases c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR and Pim-1 kinase showed that compounds 3c, 6c, 6d, 6f, 6n, 14a and 15 were the most potent of the tested compounds toward the five tyrosine kinases and compounds 3c, 6c, 6d, 6n and 15 displayed the highest inhibitions toward Pim-1 kinase.

Heterocyclization of 2-(2-phenylhydrazono)cyclohexane-1,3-dione to Synthesis Thiophene, Pyrazole and 1,2,4-triazine Derivatives with Anti-Tumor and Tyrosine Kinase Inhibitions

2020 ◽  
Vol 20 (10) ◽  
pp. 1209-1220
Author(s):  
Rafat M. Mohareb ◽  
Ensaf S. Alwan
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Tyrosine Kinases ◽  
Proliferative Activity ◽  
Cancer Cell Lines ◽  
Thiazole Derivatives ◽  
Wide Range ◽  
Cytotoxic Compounds ◽  
Triazine Derivatives ◽  
Target Molecules

Background: Recently tetrahydrobenzo[b]thiazole derivatives acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Through the market it was found that many pharmacological drugs containing the thiazole nucleus were known. Objective: This work aimed to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. The target molecules were obtained starting from the arylhydrazonocyclohexan-1,3-dione followed by their heterocyclization reactions to produce anticancer target molecules. Methods: The arylhydrazone derivatives 3a-c underwent different heterocyclization reactions to produce thiophene, thiazole, pyrazole and 1,2,4-triazine derivatives. The anti-proliferative activity of twenty six compounds among the synthesized compounds toward the six cancer cell lines namely A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721 was studied. Results: Anti-proliferative evaluations, tyrosine and Pim-1 kinase inhibitions were perform for most of the synthesized compounds where the varieties of substituent through the aryl ring and the thiophene moiety afforded compounds with high activities. Conclusion: The compounds with high anti-proliferative activity towards the cancer cell lines showed that compounds 3b, 3c, 5e, 5f, 8c, 9c, 11c, 12c, 14e, 14f and 16c were the most cytotoxic compounds. Further tests of the latter compounds toward the five tyrosine kinases c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR and Pim-1 kinase showed that compounds 3c, 5e, 5f, 8c, 9c, 12c, 14e, 14f and 16c were the most potent of the tested compounds toward the five tyrosine kinases and compounds 6d, 11a, 20b and 21e were of the highest inhibitions towards Pim-1 kinase. Pan Assay Interference Compounds (PAINS) for the most cytotoxic compounds showed zero PAINS alert and can be used as lead compounds.

New Approaches for the Synthesis of 2,3,5,6-Tetrahydrobenzo[d]thiazole Derivatives and their Anti- proliferative , c-Met Enzymatic Activity and Tyrosine Kinases Inhibitions

2021 ◽  
Vol 22 ◽  
Author(s):  
Rafat M. Mohareb ◽  
Maher H. E. Helal ◽  
Sara S. Mohamed ◽  
Amira E. M. Abdallah
Keyword(s):  
Enzymatic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tyrosine Kinases ◽  
Heterocyclic Compounds ◽  
Cancer Cell Lines ◽  
Positive Control ◽  
Thiazole Derivatives ◽  
Active Compounds

Background: Many tetrahydrobenzo[d]thiazole derivatives were considered as the most important class of heterocyclic compounds due to their biological applications. There are many drugs known in the market containing the thiazole moiety which is responsible for the high drug activity. Objective: This work aimed to produce novel heterocyclic compounds such as pyrazole, isoxazole, thiophene, chromeno[7,8-d]thiazole, and thiazolo[4,5-h]quinoline derivatives. The newly synthesized heterocyclic compounds were evaluated against anticancer cell lines followed by c-Met enzymatic activity and tyrosine kinases inhibition for the most active compounds. Methods: In this work, the 3-phenyl-2-thioxo-2,3,5,6-tetrahydrobenzo[d]thiazol-7(4H)-one (3) was synthesized through the reaction of cyclohexane-1,3-dione with phenyl isothiocyanate and elemental sulfur. Compound 3 showed interesting activity toward some chemical reagents producing new heterocyclic compounds that can’t be obtained through another way. The newly synthesized compounds were evaluated towards the six cancer cell lines. The most active compounds were selected and tested toward c-Met enzyme by taking foretinib as the positive control. Also, the inhibitions toward the PC-3 cell line using the reference SGI-1776 were measured. Finally, the inhibitions towards the five tyrosine kinases were also tested. Results: The synthesized quinoline and chromene derivatives were evaluated toward c-Met enzyme using foretinib as the positive control the obtained results showed that twelve compounds exhibited IC50 values less than 1.30 nM. On the other hand, sixteen compounds showed higher inhibitions than the reference SGI-1776 (IC50 4.86 nM) toward the PC-3 cell line. Conclusion: Novel, heterocyclic compounds were synthesized with a high impact of biological activities. All synthesized compounds were screened for their anti-proliferative effect and most of them revealed high potent effects. In addition, the c-Met and prostate cancer cell line PC-3 inhibitions for the most active compounds showed that these compounds exhibited high inhibitions. Anti-proliferative activity of selected compounds toward cancer cell lines classified according to the disease showed that most compounds exhibited high inhibitions.

Heterocyclization of 2-Arylidenecyclohexan-1,3-dione: Synthesis of Thiophene, Thiazole, and Isoxazole Derivatives with Potential Antitumor Activities

2020 ◽  
Vol 20 (3) ◽  
pp. 335-345 ◽  
Author(s):  
Nadia Y. Megally Abdo ◽  
Rafat M. Mohareb ◽  
Waleed N. Al-darkazali
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Ethyl Cyanoacetate ◽  
Structural Diversity ◽  
Cancer Cell Lines ◽  
Wide Range ◽  
High Yields ◽  
Isoxazole Derivatives

Background: Thiophene, thiazole, and isoxazole derivatives are present in a wide range of natural and synthetic compounds with heterogeneous pharmacological activity. Due to their structural diversity, they are some of the most versatile classes of compounds for anticancer drug design and discovery. Objective: Thiophene, thiazole, and isoxazole derivatives were herein designed with a dual purpose: as antiproliferative agents and kinase inhibitors. Methods: The test compounds were synthesized in moderate to high yields through a simple methodology. Tetrahydrobenzo[b]thiophen-5-one derivatives 5a-f were prepared from the reaction of 2-arylidencyclohexan- 1,3-dione 3a-c with elemental sulfur and either of malononitrile (4a) or ethyl cyanoacetate (4b) in 1,4-dioxan in the presence of triethylamine. Compounds 5a,b were used for the synthesis of thiophene, thiazole, and isoxazole derivatives through their reactions with different chemical reagents. Results: Antiproliferative evaluations, c-Met kinase, and Pim-1 kinase inhibitions were performed where some compounds revealed high activities. In all cases, antiproliferative activity and the kinase inhibitions were performed against six cancer cell lines and five tyrosine kinases, respectively. Where the most cytotoxic compounds were 3c, 5d, and 16c with IC50’s 0.29, 0.68, and 0.42μM, respectively, against the A549 cell line. Conclusion: The anti-proliferative activities of the newly synthesized compounds were evaluated against the six cancer cell lines (A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460). The most potent compounds toward the cancer cell lines (3a, 3c, 5d, 7c, 11c, 16a, and 16c) were further investigated towards the five tyrosine kinases (c-kit, FIT-3, VEGFR-2, EGFR, and PDGFR). Compounds 3c, 5d, and 16c were selected for testing of their inhibition for the Pim-1 kinase due to their anti-proliferation activities against the cancer cell lines and their high activities against the tyrosine kinases.

Microwave-assisted Synthesis of Polymethoxychalcone Mannich Bases and Their Antiproliferative Activity

2019 ◽  
Vol 16 (2) ◽  
pp. 117-121 ◽  
Author(s):  
Peipei Han ◽  
Wenhua Zhou ◽  
Mingxia Chen ◽  
Qiuan Wang
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Mannich Base ◽  
Cancer Cell Lines ◽  
Secondary Amines ◽  
Conventional Heating ◽  
Microwave Assisted ◽  
Ic50 Values ◽  
Antiproliferative Activities

A series of eight polymethoxychalcone Mannich base derivatives 2a-2h was synthesized via the microwave-assisted Mannich reaction of natural product 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1) with various secondary amines and formaldehyde. Compared to conventional heating method (80°C), the microwave-assisted method (700W, 65°C) is efficient with short reaction time (0.5-1 h) and good yields (74-88%). The antiproliferative activities of eight Mannich base derivatives were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3) by CCK-8 assay. The results showed that all of the Mannich base derivatives exhibited potential antiproliferative activities on tested cancer cell lines with the IC50 values of 9.13-48.51 µM. Some active compounds exhibited more activity as compared to positive control cis-Platin. Among them, compound 2b revealed to have the strongest antiproliferative activity against all the three cancer cell lines with IC50 values ranging from 9.13 to 11.24 µM.

scholarly journals Underutilized Mexican Plants: Screening of Antioxidant and Antiproliferative Properties of Mexican Cactus Fruit Juices

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 368
Author(s):  
Elda M. Melchor Martínez ◽  
Luisaldo Sandate-Flores ◽  
José Rodríguez-Rodríguez ◽  
Magdalena Rostro-Alanis ◽  
Lizeth Parra-Arroyo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
In Vitro Assays ◽  
Total Phenolic ◽  
Liver Cancer Cell ◽  
Antiproliferative Activities

Cacti fruits are known to possess antioxidant and antiproliferative activities among other health benefits. The following paper evaluated the antioxidant capacity and bioactivity of five clarified juices from different cacti fruits (Stenocereus spp., Opuntia spp. and M. geomettizans) on four cancer cell lines as well as one normal cell line. Their antioxidant compositions were measured by three different protocols. Their phenolic compositions were quantified through high performance liquid chromatography and the percentages of cell proliferation of fibroblasts as well as breast, prostate, colorectal, and liver cancer cell lines were evaluated though in vitro assays. The results were further processed by principal component analysis. The clarified juice from M. geomettizans fruit showed the highest concentration of total phenolic compounds and induced cell death in liver and colorectal cancer cells lines as well as fibroblasts. The clarified juice extracted from yellow Opuntia ficus-indica fruit displayed antioxidant activity as well as a selective cytotoxic effect on a liver cancer cell line with no toxic effect on fibroblasts. In conclusion, the work supplies evidence on the antioxidant and antiproliferative activities that cacti juices possess, presenting potential as cancer cell proliferation preventing agents.

scholarly journals Correction: Colchicine metallocenyl bioconjugates showing high antiproliferative activities against cancer cell lines

2018 ◽  
Vol 47 (8) ◽  
pp. 2822-2822 ◽  
Author(s):  
Karolina Kowalczyk ◽  
Andrzej Błauż ◽  
Wojciech M. Ciszewski ◽  
Anna Wieczorek ◽  
Błażej Rychlik ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Dalton Trans ◽  
Antiproliferative Activities

Correction for ‘Colchicine metallocenyl bioconjugates showing high antiproliferative activities against cancer cell lines’ by Karolina Kowalczyk et al., Dalton Trans., 2017, 46, 17041–17052.

scholarly journals Synthesis and Biological Activity of 2-Arylidene-N-(quinolin-6-yl)hydrazine-1-carboxamides

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shengxian Zhao ◽  
Yin Cao ◽  
Zhenzhen Cui ◽  
Jiayun Zhang ◽  
Zhixiang Pan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Colony Formation Assay ◽  
M Phase ◽  
Antiproliferative Activities ◽  
Mcf 7

A series of 2-arylidene-N-(quinolin-6-yl)hydrazine-1-carboxamides 5a–5o were synthesized and characterized. The synthesized compounds (5a–5o) were screened in vitro against three breast cancer cell lines: SKBR3, MDA-MB-231, and MCF-7 cancer cell lines by the MTT assay. According to MTT results, compounds 5k and 5l showed better antiproliferative activities over MCF-7 cell lines with IC50 values of 8.50 and 12.51 μM. Colony formation assay indicated 5k/5l treatment obviously inhibited the growth of MCF-7 cells and 5k/5l-induced cell cycle was arrested in the G2-M phase. Moreover, 5k/5l significantly increased the level of cleaved PARP and induced the apoptosis in MCF-7 cells. In addition, compared to Hela cells, MCF-7 cells were more sensitive to 5k/5l treatment.

scholarly journals A New Cytotoxic Tetrahydroxanthene-1,3(2H)-dione Derivative from Uvaria cordata and Structure Revision of Valderramenol A

2018 ◽  
Vol 13 (5) ◽  
pp. 1934578X1801300
Author(s):  
Duc Viet Ho ◽  
Hung Quoc Vo ◽  
Tho Huu Nguyen ◽  
Thao Thi Do ◽  
Hoai Thi Nguyen
Keyword(s):  
Theoretical Calculation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Viet Nam ◽  
Free Energies ◽  
Hep G2 ◽  
Spectroscopic Analyses ◽  
Dione Derivative ◽  
Structure Revision

A new tetrahydroxanthene-1,3(2H)-dione derivative (1) was isolated from the leaves of Uvaria cordata collected in Viet Nam. Its structure was elucidated to be a mixture of four tautomers (1a–1d) by a combination of extensive spectroscopic analyses and the theoretical calculation of Gibbs free energies. Compound 1 exhibited moderate cytotoxicity against KB, LNCaP, Hep-G2, MKN-7, SW-480, HL-60, and SK-Mel-2 cancer cell lines with IC50 values ranging from 25.92 ± 2.33 to 44.29 ± 4.36 μg/mL. In addition, the previously reported structure of valderramenol A has been revised to 1a/1b.

Sign in / Sign up

Export Citation Format

Share Document