scholarly journals Design, Synthesis, and Antipoliferative Activities of Novel Substituted Imidazole-Thione Linked Benzotriazole Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5983
Author(s):  
Ahdab N. Khayyat ◽  
Khaled O. Mohamed ◽  
Azizah M. Malebari ◽  
Afaf El-Malah
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Tubulin Polymerization ◽  
Design Synthesis ◽  
Biological Studies ◽  
Phase Compound ◽  
Hct 116 ◽  
Mcf 7

A new series of benzotriazole moiety bearing substituted imidazol-2-thiones at N1 has been designed, synthesized and evaluated for in vitro anticancer activity against the different cancer cell lines MCF-7(breast cancer), HL-60 (Human promyelocytic leukemia), and HCT-116 (colon cancer). Most of the benzotriazole analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, BI9 showed potent activity against the cancer cell lines such as MCF-7, HL-60 and HCT-116 with IC50 3.57, 0.40 and 2.63 µM, respectively. Compound BI9 was taken up for elaborate biological studies and the HL-60 cells in the cell cycle were arrested in G2/M phase. Compound BI9 showed remarkable inhibition of tubulin polymerization with the colchicine binding site of tubulin. In addition, compound BI9 promoted apoptosis by regulating the expression of pro-apoptotic protein BAX and anti-apoptotic proteins Bcl-2. These results provide guidance for further rational development of potent tubulin polymerization inhibitors for the treatment of cancer.

scholarly journals Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3923
Author(s):  
Adel A.-H. Abdel-Rahman ◽  
Amira K. F. Shaban ◽  
Ibrahim F. Nassar ◽  
Dina S. EL-Kady ◽  
Nasser S. M. Ismail ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines ◽  
Hct 116 ◽  
Mcf 7

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

scholarly journals Synthesis, Anticancer Activity, and Molecular Modeling of New Halogenated Spiro[pyrrolidine-thiazolo-oxindoles] Derivatives

2020 ◽  
Vol 10 (6) ◽  
pp. 2170 ◽  
Author(s):  
Mohammad Shahidul Islam ◽  
Abdullah Mohammed Al-Majid ◽  
Fardous F. El-Senduny ◽  
Farid A. Badria ◽  
A. F. M. Motiur Rahman ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Single Step ◽  
One Pot ◽  
Antiproliferative Effects ◽  
Physiochemical Parameters ◽  
Hct 116 ◽  
Mcf 7

A one-pot, single-step, and an atom-economical process towards the synthesis of highly functionalized spirooxindoles analogues was efficiently conducted to produce a satisfactory chemical yields (70–93%) with excellent relative diastereo-, and regio-selectivity. An in vitro antiproliferative assay was carried out on different cancer cell lines to evaluate the biological activity of the synthesized tetrahydro-1’H-spiro[indoline-3,5’-pyrrolo[1,2-c]thiazol]-2-one 5a–n. The prepared hybrids were then tested in vitro for their antiproliferative effects against three cancer cell lines, namely, HepG2 (liver cancer), MCF-7 (breast cancer), and HCT-116 (colon cancer). The spirooxindole analogue 5g exhibited a broad activity against HepG2, MCF-7, and HCT-116 cell lines of liver, breast, and colorectal cancers when compared to cisplatin. Modeling studies including shape similarity, lipophilicity scores, and physicochemical parameters were calculated. The results of this study indicated that spirooxindole analogue 5g retained a good physiochemical parameters with acceptable lipophilicity scores.

Cytotoxicity , docking study of new fluorinated fused pyrimidine scaffold: Thermal and microwave irradiation synthesis

2019 ◽  
Vol 16 ◽  
Author(s):  
Alaa M. Abo Alnaja ◽  
Thoraya. A. Farghaly ◽  
Heba S. A. El-zahabi ◽  
Mohamed R. Shaaban
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Microwave Irradiation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Hepatic Cancer ◽  
Hct 116 ◽  
Mcf 7

Background: Azolopyrimidines are imposed on the arena of drugs treated for cancer. The urgent need to discover new selective anticancer agents, paved the way to explore the antitumor significance of such fused systems. From synthetic point of view, Microwave- facilitated technique for synthesis is very strongly associated with green method in chemistry field. Aim: Our aim is to synthesis of bioactive compounds and using docking simulation run by MOE program to explore the binding mode of the most active enzyme inhibitor among the target compounds. Method: In addition to the use of conventional heating, the MARS system of CEM utilized for Microwave irradiation that is equipped with a multi-mode platform with a magnetic stirring plate and a rotor that allows the parallel processing of many vessels per batch. All the synthesized compounds were tested for their anticancer activity against hepatic cancer (HePG-2), breast cancer (MCF-7) and colon cancer (HCT-116). Screening against the cancer cell lines was performed, using doxorubicin as a reference drug. Docking studies were conducted using MOE software. Result: A novel series of fluorinated fused-pyrimidine namely, pyrazolopyrimidine, triazolopyrimidine and pyrimidobenzimidazole were designed and synthesized conventionally and under microwave irradiations The mechanistic pathways as well as the structure of all products were debated and demonstrated based on all possible spectral data. In-vitro examination of the novel prepared derivatives versus the three different human cancer cell lines [hepatic cancer (HePG-2), breast cancer (MCF-7) and colon cancer (HCT-116)] was evaluated to estimate their actual activity. Conclusion: We have developed a simple, facile, and efficient procedure for the formation of new series of azolopyrimidines. All spectra of all products were investigated deliberately to confirm their structures. The anti-cancer activity has been examined against three cancer cell lines e.g. HepG-2, MCF-7 and HCT116. Molecular modeling study was carried out in order to rationalize the in vitro anti-tumor results.

Design, Synthesis and Cytotoxicity of Novel Coumarin-1,2,3-triazole-1,2,4- Oxadiazole Hybrids as Potent Anti-breast Cancer Agents

2019 ◽  
Vol 16 (7) ◽  
pp. 818-824 ◽  
Author(s):  
Maryam Mohammadi-Khanaposhtani ◽  
Kiana Fahimi ◽  
Elahe Karimpour-Razkenari ◽  
Maliheh Safavi ◽  
Mohammad Mahdavi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Click Reaction ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Design Synthesis ◽  
Mcf 7

Background: This work reports design, synthesis, and in vitro cytotoxicity of novel coumarin-1,2,3-triazole-1,2,4-oxadiazole hybrids against three breast cancer cell lines MCF-7, MDA-MB-231, and T-47D. Methods: Synthetic procedure for the preparation of desired compounds was started from the reaction of coumarins or with propargyl bromide to give O-propargylated coumarins or 5. Then, click reaction between the later compounds and 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles afforded the desired products in good yields. Results: Among the synthesized compounds, 4-((1-((3-(4-chlorophenyl)-1,2,4-oxadiazol-5- yl)methyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (9a) showed the best cytotoxicity against breast cancer cell lines. Conclusion: Compound 9a depicted the most activity toward MDA-MB-231 and T-47D cells while compounds 8a and 8c were the most potent compounds against MCF-7.

In Vitro Antitumor Evaluation of Some Hybrid Molecules Containing Coumarin and Quinolinone Moieties

2020 ◽  
Vol 19 (16) ◽  
pp. 2010-2018
Author(s):  
Youstina W. Rizzk ◽  
Ibrahim M. El-Deen ◽  
Faten Z. Mohammed ◽  
Moustafa S. Abdelhamid ◽  
Amgad I.M. Khedr
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Cancer Cell Lines ◽  
Bax Protein ◽  
Hybrid Molecules ◽  
Mcf 7

Background: Hybrid molecules furnished by merging two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery. Currently, coumarin hybrids have attracted the keen attention of researchers to discover their therapeutic capability against cancer. Objective: The present study aimed to evaluate the in vitro antitumor activity of a new series of hybrid molecules containing coumarin and quinolinone moieties 4 and 5 against four cancer cell lines. Materials and Methods: A new series of hybrid molecules containing coumarin and quinolinone moieties, 4a-c and 5a-c, were synthesized and screened for their cytotoxicity against prostate PC-3, breast MCF-7, colon HCT- 116 and liver HepG2 cancer cell lines as well as normal breast Hs-371 T. Results: All the synthesized compounds were assessed for their in vitro antiproliferative activity against four cancer cell lines and several compounds were found to be active. Further in vitro cell cycle study of compounds 4a and 5a revealed MCF-7 cells arrest at G2 /M phase of the cell cycle profile and induction apoptosis at pre-G1 phase. The apoptosis-inducing activity was evidenced by up-regulation of Bax protein together with the downregulation of the expression of Bcl-2 protein. The mechanism of cytotoxic activity of compounds 4a and 5a correlated to its topoisomerase II inhibitory activity. Conclusion: Hybrid molecules containing coumarin and quinolinone moieties represents a scaffold for further optimization to obtain promising anticancer agents.

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 In vitro investigation of cytotoxic and antioxidative activities of Ardisia crispa against breast cancer cell lines, MCF-7 and MDA-MB-231

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Muhammad Luqman Nordin ◽  
Arifah Abdul Kadir ◽  
Zainul Amiruddin Zakaria ◽  
Rasedee Abdullah ◽  
Muhammad Nazrul Hakim Abdullah
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
In Vitro Investigation ◽  
Ardisia Crispa ◽  
Mcf 7

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 Cytotoxic Constituents of Pachyrhizus Tuberosus from Peruvian Amazon

2013 ◽  
Vol 8 (10) ◽  
pp. 1934578X1300801 ◽  
Author(s):  
Olga Leuner ◽  
Jaroslav Havlik ◽  
Milos Budesinsky ◽  
Vladimir Vrkoslav ◽  
Jessica Chu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Mtt Assay ◽  
Human Cancer ◽  
Chemical Constituents ◽  
Human Fibroblasts ◽  
Cancer Cell Lines ◽  
Cytotoxic Effects ◽  
Hct 116 ◽  
Mcf 7

Investigations into the chemical constituents of the seeds of the neglected tuber crop Pachyrhizus tuberosus (Leguminosae) resulted in the isolation of seven components: five rotenoids [12a-hydroxyerosone (1), 12a-hydroxydolineone (2), erosone (3), 12a-hydroxyrotenone (4) and rotenone (6)], a phenylfuranocoumarin [pachyrrhizine (5)] and an isoflavanone [neotenone (7)]. The compounds were isolated using several chromatography techniques and characterized and verified by NMR and HPLC/MS. The MTT assay was used to examine the selective cytotoxic effects of the methanolic P. tuberosus extract and isolated compounds in two human cancer cell lines [breast (MCF-7) and colorectal (HCT-116)] and in non-transformed human fibroblasts (MRC-5); IC50 values were calculated. The methanolic P. tuberosus extract displayed respectable cytotoxic effects against HCT-116 and MCF-7 cells with IC50 values of 7.3 and 6.3 μg/mL, respectively. Of the compounds, 6 exacted greatest cytotoxicity and selectivity towards the cancer cell lines tested, yielding IC50 values of 0.3 μg/mL against both MCF-7 and HCT-116 cells, and a 6-fold reduced activity against MRC-5 fibroblasts. Compound 4 also demonstrated cytotoxicity against MCF-7 and HCT-116 (1.1 and 1.8 μg/mL, respectively), and reduced cytotoxicity towards MRC-5 cells (7.5 μg/mL). The results revealed from the in vitro cytotoxic MTT assay are worthy of further antitumor investigation.

Sign in / Sign up

Export Citation Format

Share Document