scholarly journals Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response

RSC Advances ◽  
2018 ◽  
Vol 8 (43) ◽  
pp. 24376-24385 ◽  
Author(s):  
Wen-Bin Kuang ◽  
Ri-Zhen Huang ◽  
Yi-Lin Fang ◽  
Gui-Bin Liang ◽  
Chen-Hui Yang ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Antitumor Agents ◽  
Quinoline Derivatives ◽  
Apoptotic Response ◽  
Design Synthesis ◽  
Cycle Arrest ◽  
In Vivo Antitumor Activity ◽  
Combination Principle

A series of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives were designed and synthesized as antitumor agents under the combination principle. The antitumor activity and mechanisms were then evaluated.

Tubulin Inhibitors Binding to Colchicine-Site: A Review from 2015 to 2019

2020 ◽  
Vol 27 (40) ◽  
pp. 6787-6814 ◽  
Author(s):  
Lin-Ying Xia ◽  
Ya-Liang Zhang ◽  
Rong Yang ◽  
Zhong-Chang Wang ◽  
Ya-Dong Lu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Antitumor Agents ◽  
Structural Features ◽  
Design Synthesis ◽  
Antiproliferative Effects ◽  
Tubulin Inhibitors ◽  
Relationship Of ◽  
Podophyllotoxin Derivatives

Due to the three domains of the colchicine-site which is conducive to the combination with small molecule compounds, colchicine-site on the tubulin has become a common target for antitumor drug development, and accordingly, a large number of tubulin inhibitors binding to the colchicine-site have been reported and evaluated over the past years. In this study, tubulin inhibitors targeting the colchicine-site and their application as antitumor agents were reviewed based on the literature from 2015 to 2019. Tubulin inhibitors were classified into ten categories according to the structural features, including colchicine derivatives, CA-4 analogs, chalcone analogs, coumarin analogs, indole hybrids, quinoline and quinazoline analogs, lignan and podophyllotoxin derivatives, phenothiazine analogs, N-heterocycle hybrids and others. Most of them displayed potent antitumor activity, including antiproliferative effects against Multi-Drug-Resistant (MDR) cell lines and antivascular properties, both in vitro and in vivo. In this review, the design, synthesis and the analysis of the structure-activity relationship of tubulin inhibitors targeting the colchicine-site were described in detail. In addition, multi-target inhibitors, anti-MDR compounds, and inhibitors bearing antitumor activity in vivo are further listed in tables to present a clear picture of potent tubulin inhibitors, which could be beneficial for medicinal chemistry researchers.

scholarly journals Indolo[2,3-b]quinoline derivatives as novel promising antitumor agents

2016 ◽  
Author(s):  
Lukasz Kaczmarek ◽  
Katarzyna Badowska-Rosłonek ◽  
Anna Jaromin ◽  
Wojciech Łuniewski ◽  
Wanda Peczyńska-Czoch ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Topoisomerase Ii ◽  
Antitumor Agents ◽  
Aqueous Media ◽  
Human Tumors ◽  
Quinoline Derivatives ◽  
Dna Topoisomerase ◽  
Cryptolepis Sanguinolenta

In the search for novel antineoplastic compounds we have found that four-membered, linear 5,11-dimethyl -5H- indolo[2,3-b]quinoline (DIMIQ) reveals cytostatic activity in vitro and moderate antitumor activity in vivo in mice melanoma B16 as well as leukemias L1210 and P388. Preliminary studies showed that DIMIQ stabilizes DNA-topoisomerase II complex. Some years later indolo[2,3-b]quinoline was found as an alkaloid neocryptolepine in the West African shrub Cryptolepis sanguinolenta. Unfortunately, DIMIQ’s high toxicity, lack of selectivity and very low solubility in aqueous media seriously limit the practical use of this compound as an anticancer drug. Extensive research on the structure-activity relationships of different indolo[2,3-b]quinoline derivatives showed that the position and type of the substituent is conclusive both to the antitumor activity and general toxicity of the compound. These studies led us to discover derivatives of DIMIQ which exhibit very low toxicity against normal cells and are highly toxic against selected human tumors. These derivatives are soluble in water and some of them are able to overcome multidrug resistance in human tumors cells.

scholarly journals Indolo[2,3-b]quinoline derivatives as novel promising antitumor agents

2016 ◽  
Author(s):  
Lukasz Kaczmarek ◽  
Katarzyna Badowska-Rosłonek ◽  
Anna Jaromin ◽  
Wojciech Łuniewski ◽  
Wanda Peczyńska-Czoch ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Topoisomerase Ii ◽  
Antitumor Agents ◽  
Aqueous Media ◽  
Human Tumors ◽  
Quinoline Derivatives ◽  
Dna Topoisomerase ◽  
Cryptolepis Sanguinolenta

In the search for novel antineoplastic compounds we have found that four-membered, linear 5,11-dimethyl -5H- indolo[2,3-b]quinoline (DIMIQ) reveals cytostatic activity in vitro and moderate antitumor activity in vivo in mice melanoma B16 as well as leukemias L1210 and P388. Preliminary studies showed that DIMIQ stabilizes DNA-topoisomerase II complex. Some years later indolo[2,3-b]quinoline was found as an alkaloid neocryptolepine in the West African shrub Cryptolepis sanguinolenta. Unfortunately, DIMIQ’s high toxicity, lack of selectivity and very low solubility in aqueous media seriously limit the practical use of this compound as an anticancer drug. Extensive research on the structure-activity relationships of different indolo[2,3-b]quinoline derivatives showed that the position and type of the substituent is conclusive both to the antitumor activity and general toxicity of the compound. These studies led us to discover derivatives of DIMIQ which exhibit very low toxicity against normal cells and are highly toxic against selected human tumors. These derivatives are soluble in water and some of them are able to overcome multidrug resistance in human tumors cells.

scholarly journals Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said
Keyword(s):  
Molecular Modeling ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin

2014 ◽  
Vol 74 ◽  
pp. 742-750 ◽  
Author(s):  
Chengyuan Liang ◽  
Juan Xia ◽  
Dong Lei ◽  
Xiang Li ◽  
Qizheng Yao ◽  
...  
Keyword(s):  
Schiff Base ◽  
Antitumor Activity ◽  
Schiff Base Derivatives ◽  
In Vivo Antitumor Activity ◽  
Derivatives Of

„IN VITRO“ AND „IN VIVO“ ANTITUMOR ACTIVITY OF PLATINUM(II) COMPLEXES WITH MALONIC ACID ON BREAST AND COLORECTAL CARCINOMA CELL LINES

2021 ◽  
Author(s):  
Andjela Franich ◽  
◽  
Milica Dimitrijević Stojanović ◽  
Snežana Rajković ◽  
Marina Jovanović ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Colorectal Carcinoma ◽  
Cell Lines ◽  
Tumor Model ◽  
Carcinoma Cells ◽  
Spectroscopic Techniques ◽  
Murine Cell Line ◽  
In Vivo Antitumor Activity

Four Pt(II) complexes of the general formula [Pt(L)(5,6-epoxy-1,10-phen)], where L is anion of malonic (mal, Pt1), 2-methylmalonic (Me-mal, Pt2), 2,2-dimethylmalonic (Me2-mal, Pt3) or 1,1- cyclobutanedicarboxylic (CBDCA, Pt4) acid while 5,6-epoxy-1,10-phen is bidentately coordinated 5,6-epoxy-5,6-dihydro-1,10-phenanthroline were synthesized and characterized by elemental microanalysis, IR, UV-Vis and NMR (1H and 13C) spectroscopic techniques. In vitro anticancer activity of novel platinum(II) complexes have been investigated on human and murine cancer cell lines, as well as normal murine cell line by MTT assay. The obtained results indicate that studied platinum(II) complexes exhibited strong cytotoxic activity against murine breast carcinoma cells (4T1), human (HCT116) and murine (CT26) colorectal carcinoma cells. Complex Pt3 display stronger selectivity toward carcinoma cells in comparison to other tested platinum(II) complexes exhibiting beneficial antitumor activity mainly via the induction of apoptosis, as well as inhibition of cell proliferation and migration. Further study showed that Pt3 complex also carry significant in vivo antitumor activity in orthotopical 4T1 tumor model without detected liver, kidney, lung, and heart toxicity. All results imply that these novel platinum(II) complexes have a good anti-tumor effect on breast and colorectal cancer in vivo and in vitro and the affinity to become possible candidates for treatment in anticancer therapy.

Copper complexes as antitumor agents: in vitro and in vivo evidences

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucia M. Balsa ◽  
Enrique J. Baran ◽  
Ignacio E. León
Keyword(s):  
Copper Complexes ◽  
Antitumor Agents ◽  
Essential Element ◽  
Design Synthesis ◽  
Copper Compounds ◽  
Comprehensive Knowledge ◽  
The Relationship

: Copper is an essential element for most aerobic organisms, with an important function as a structural and catalytic cofactor, and in consequence, it is implicated in several biological actions. The relevant aspects of chemistry and biochemistry and the importance of copper compounds in medicine give us a comprehensive knowledge of the multifaceted applications of copper in physiology and physiopathology. In this review, we present an outline of the chemistry and the antitumor properties of copper complexes on breast, colon, and lung cancer cells focus on the role of copper in cancer, the relationship between structure-activity, molecular targets, and the study of the mechanism of action involved in its anticancer activity. This overview is expected to contribute to understanding the design, synthesis, uses of copper complexes as antitumor agents in the most common cancers.

Cytotoxicity and Antitumor Activity of Platinum(II) Complexes of Aromatic and Cycloalkanecarboxylic Acid Hydrazides

1997 ◽  
Vol 52 (1-2) ◽  
pp. 49-54 ◽  
Author(s):  
Daniel N. Kushev ◽  
Nadejda C. Spassovska ◽  
Svetoslav I. Taxirov ◽  
Konstantin C. Grancharov
Keyword(s):  
Antitumor Activity ◽  
Acid Hydrazide ◽  
In Vitro Cytotoxicity ◽  
Macromolecular Synthesis ◽  
H Nmr ◽  
Antineoplastic Effect ◽  
In Vivo Antitumor Activity ◽  
Friend Leukemia

AbstractNew platinum(II) complexes of cyclohexanecarboxylic acid hydrazide (chcah) were synthesized and characterized by elemental analysis, IR. and 1H NMR spectra. Their inhibitory effects on cell growth and macromolecular synthesis of Friend leukemia cells in culture as well as the in vivo antitumor activity towards L1210 leukemia in mice were compared with those of complexes containing differently substituted aromatic acid hydrazides. Some of the complexes exhibited antineoplastic activity. No correlation between the in vitro cytotoxicity and the in vivo antitumor activity was found. However, there was a relationship between the in vitro macromolecular synthesis inhibition profile and the in vivo antineoplastic effect, similar to that of cisplatin. On the other hand, only agents containing one ammine ligand were active in vivo. The substitution of the aromatic ring by a cycloalkane residue increased significantly the antitumor effect, with [Pt(NH3)(chcah)Cl2] being the most active compound in this study.

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