Development of New Potential Anticancer Metal Complexes Derived from 2-Hydrazinobenzothiazole

2019 ◽  
Vol 19 (11) ◽  
pp. 913-922 ◽  
Author(s):  
Shadia A. Elsayed ◽  
Entsar A. Saad ◽  
Sahar I. Mostafa
Keyword(s):  
Side Effects ◽  
Dna Binding ◽  
Metal Complexes ◽  
Anticancer Agents ◽  
High Efficiency ◽  
Human Cancer ◽  
Binding Ability ◽  
Oxidation Activity ◽  
Hct 116 ◽  
Mcf 7

Background: Due to the side effects of clinically approved anticancer drugs there is a great need to explore and develop new metal-based anticancer drug molecules of high efficiency with less or no side effects. Objective: To synthesize new metal complexes of 2-hydrazinobenzothiazole (hbt) and to investigate their potential anticancer characteristics. Methods: New five complexes; [VO(hbt)2SO4].4H2O (1), [Ru(hbt)2Cl3(H2O)] (2), [M(hbt)2Cl2] [M(II) = Pd (3), Pt (4)] and [Ag(hbt)2].NO3 (5) were prepared and their structure was investigated by means of FTIR, 1H NMR, ESI-MS and UV-Vis spectra, elemental and thermal analysis, magnetic and molar conductance measurements. The ligand and its complexes were examined as anticancer agents against Ehrlich ascites carcinoma (EAC) and human cancer cells (hepatocellular carcinoma Hep-G2, mammary gland breast cancer MCF-7 and colorectal carcinoma HCT-116). This feature is further supported by the DNAmetal complexes binding ability. In addition, anti-oxidation activity of the complexes was investigated. Results: Complex (5) shows the highest anticancer activity with IC50 of 5.15, 9.9, 13.1 and 17.7 µg/mL for EAC, HePG-2, MCF-7 and HCT-116, respectively. Complexes (2) and (3) show promising cytotoxicity against EAC and HePG-2 cells with IC50 5.49 and 16.2 µg/mL, respectively. While, complexes (1) and (4) show optimistic cytotoxicity against EAC with IC50 of 9.63 and 11.25 µg/mL, respectively. The order of DNA binding ability of the complexes is (5) > (3) > (2) > (1) > (4). Among the five complexes, complex (5) shows the best anti-oxidation activity. Conclusion: Complex (5) showed the highest DNA binding ability, anti-oxidation and anticancer activities.

Evaluation of Pyrano[3,2 C] Quinoline Analogues as Anticancer Agents

2019 ◽  
Vol 19 (10) ◽  
pp. 1285-1292 ◽  
Author(s):  
Kuldip D. Upadhyay ◽  
Anamik K. Shah
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Biological Activities ◽  
Cytotoxic Agents ◽  
Tumor Growth Inhibition ◽  
Mice Model ◽  
One Pot ◽  
Aryl Ring ◽  
Hct 116

Background: Quinoline analogues exhibited diversified biological activities depending on the structure type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes were reported as promising cytotoxic agents. Objective: The present study is aimed to evaluate a new series of pyrano[3,2-c]quinoline scaffolds derived from the fusion of bioactive quinolone pharmacophore with structurally diverse aryl substituted chromene for its cytotoxicity. Methods: A library of pyrano[3,2-c]quinoline analogues was prepared from one-pot multi component synthesis using various aromatic aldehydes, malononitrile and 2,4-dihydroxy-1-methylquinoline. The new synthetics were primarily screened for its cytotoxicity (IC50) against different human cancer cell lines in vitro. The promising synthetics were further evaluated in vitro for their potency against different kinase activity. The promising compounds were finally tested for their in vivo efficacy in SCID type mice HCT-116 tumor model. Results: The screening results revealed that compounds 4c, 4f, 4i and 4j showed promising activity in in vitro study. However, compound 4c was found to be the most potent candidate with 23% tumor growth inhibition in HCT-116 tumor mice model. Conclusion: The structure activity relationship suggested that 3-substitution on the aryl ring at C4 position of the pyrano[3,2 c]quinolone moiety seems to have an important position for cytotoxicity activity. However, 3- chloro substitution at C4 aryl ring showed a significant alteration of the bioactive conformer of the parent scaffold and outcome with compound 4c as the most potent candidate of the series.

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.

Synthesis and antiproliferative and c-Src kinase inhibitory activities of cinnamoyl- and pyranochromen-2-one derivatives

2013 ◽  
Vol 91 (8) ◽  
pp. 741-754 ◽  
Author(s):  
Karam Chand ◽  
Amir Nasrolahi Shirazi ◽  
Preeti Yadav ◽  
Rakesh K. Tiwari ◽  
Meena Kumari ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Human Cancer ◽  
Src Kinase ◽  
Cancer Cell Lines ◽  
Ovarian Adenocarcinoma ◽  
Human Cancer Cell Lines ◽  
Mcf 7

A series of 6- and 8-cinnamoylchromen-2-one and dihydropyranochromen-2-one derivatives were synthesized and their antiproliferative activities were evaluated against three human cancer cell lines, i.e., ovarian adenocarcinoma (SK-OV-3), leukemia (CCRF-CEM), and breast carcinoma (MCF-7). In general, 8-cinnamoylchromen-2-one derivatives were found to have higher antiproliferative activity against the cancer cells when compared with 6-cinnamoyl analogues. Among all of the hybrid chromen-2-one − chalcone/flavanone compounds, a 7-hydroxy-8-cinnamoylchromen-2-one derivative 35 was found to be consistently active against all the cancer cell lines and inhibited the cell proliferation of SK-OV-3, CCRF-CEM, and MCF-7 by 63%, 50%, and 43%, respectively, at a concentration of 50 μmol/L after 72 h of incubation. This compound also exhibited the highest Src kinase inhibition (IC50 = 14.5 μmol/L). Structure−activity relationship studies provided insights for designing the next generation of chromen-2-one − chalcone hybrid prototypes and the development of new leads as anticancer agents and (or) Src kinase inhibitors.

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.

scholarly journals In Vitro Antioxidant evaluation and DNA binding ability of Ni(II), Co(II), Cu(II) and Zn(II) metal complexes containing bidentate Schiff base

2017 ◽  
Vol 10 (3) ◽  
pp. 06-14
Author(s):  
Mohammad Ibrahim ◽  
Asif Khan ◽  
Bushra Faiz ◽  
Muhammad Ikram ◽  
HazratUn Nabi ◽  
...  
Keyword(s):  
Schiff Base ◽  
Dna Binding ◽  
Metal Complexes ◽  
Binding Ability ◽  
Antioxidant Evaluation

scholarly journals High pressure assisted synthetic approach for novel 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline derivatives and their assessment as anticancer agents

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Haider Behbehani ◽  
Fatemah A. Aryan ◽  
Kamal M. Dawood ◽  
Hamada Mohamed Ibrahim
Keyword(s):  
Colon Cancer ◽  
High Pressure ◽  
Cancer Cells ◽  
Colorimetric Assay ◽  
Human Cancer ◽  
Conventional Heating ◽  
Synthetic Approach ◽  
Quinoline Derivatives ◽  
Hct 116 ◽  
Mcf 7

AbstractA novel, expedient and effective methodology for the synthesis of distinctly substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline systems has been developed with a new synthetic platform. This process includes ammonium acetate-mediated cyclocondensation reactions of 3-oxo-2-arylhydrazonopropanals with benzosuberone and tetralone precursors, respectively, using the high-pressure Q-tube reactor, which has been found to be superior to both conventional heating and microwave irradiation. The novel protocol benefits from its high atom efficiency, economy, ease of workup, broad substrate scope and is also applicable to gram-scale synthesis. To identify and confirm the newly synthesized targeted compounds, the X-ray single-crystal as well as all possible spectroscopic methods were utilized. The cytotoxicity of the newly synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j and 5,6-dihydrobenzo-[h]quinolines derivatives 6a–e were preliminary examined toward three cell lines of human cancer; lung cancer (A549), breast cancer (MCF-7) and colon cancer (HCT-116), by applying the MTT colorimetric assay. The achieved results reflected the promising profile of the prepared compounds in this study against cancer cells and have shown that members from the synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j exhibited promising cytotoxicity’s against MCF-7, and A549 cancer cells respectively, while the HCT-116 (colon) cancer cells were inhibited by certain examples of 5,6-dihydrobenzo[h]quinoline derivatives 6c,d. These promising results could serve as a good primary base for further research into the design of anticancer drugs.

Synthesis, DNA-Binding Ability and Biological Activity of C8 Linked G1 Dendrimer-Pyrrolobenzodiazepine Conjugates as Anticancer Agents

2008 ◽  
Vol 5 (7) ◽  
pp. 424-432 ◽  
Author(s):  
Ahmed Kamal ◽  
G. Balakishan ◽  
Rajender ◽  
K. Sreekanth ◽  
D. Rajasekhar Reddy ◽  
...  
Keyword(s):  
Biological Activity ◽  
Dna Binding ◽  
Anticancer Agents ◽  
Binding Ability

scholarly journals One-Pot Multicomponent Synthesis and Cytotoxic Evaluation of Novel 7-Substituted-5-(1H-Indol-3-yl)Tetrazolo[1,5-a] Pyrimidine-6-Carbonitrile

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 255
Author(s):  
Mohamed A. A. Radwan ◽  
Fahad M. Alminderej ◽  
Hanem M. Awad
Keyword(s):  
Human Cancer ◽  
Human Colon ◽  
Human Lung Cancer ◽  
Multicomponent Synthesis ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
One Pot ◽  
Human Cancer Cell Lines ◽  
Hct 116 ◽  
Mcf 7

A series of novel 7-substituted-5-(1H-indol-3-yl)tetrazolo[1,5-a]pyrimidine-6-carbonitrile was synthesized via a one-pot, three-multicomponent reaction of appropriate aldehydes, 1H-tetrazole-5-amine and 3-cyanoacetyl indole in catalytic triethylamine. The cytotoxic activity of the new synthesized tetrazolopyrimidine-6-carbonitrile compounds was investigated against HCT-116, MCF-7, MDA-MB-231, A549 human cancer cell lines and one human healthy normal cell line (RPE-1) using the MTT cytotoxicity assay. Compounds 4h, 4b, 4c, 4i and 4a showed potent anticancer activities against human colon cancer. Additionally, all the compounds showed potent anticancer activities on human lung cancer.

scholarly journals Synthesis and Cytotoxic Activity of New 1,3,4-Thiadiazole Thioglycosides and 1,2,3-Triazolyl-1,3,4-Thiadiazole N-glycosides

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3738 ◽  
Author(s):  
Alminderej ◽  
Elganzory ◽  
El-Bayaa ◽  
Awad ◽  
El-Sayed
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
Breast Adenocarcinoma ◽  
Cytotoxic Activities ◽  
Acetylenic Derivative ◽  
Thiol Compounds ◽  
Reference Drug ◽  
Human Cancer Cells ◽  
Hct 116 ◽  
Mcf 7

New 1,3,4-thiadiazole thioglycosides linked to substituted arylidine systems were synthesized via glycosylation of the prepared 1,3,4-thiadiazole thiol compounds. Click strategy was also used for the synthesis of new 1,3,4-thiadiazole and 1,2,3-triazole hybrid glycosides by reaction of the acetylenic derivatives with different glycosyl azids followed by deacetylation process. The cytotoxic activities of the prepared compounds were studied against HCT-116 (human colorectal carcinoma) and MCF-7 (human breast adenocarcinoma) cell lines using the MTT assay. The results showed that the key thiadiazolethione compounds 2 and 3, the triazole glycosides linked to p-methoxyarylidine derivatives 14 and 15 in addition to the free hydroxyl glycoside 20 were found potent in activity comparable to the reference drug doxorubicin against MCF-7 human cancer cells. The acetylenic derivative 2 and glycoside 20 were also found highly active against HCT-116 cell lines.

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