Design, synthesis and potential anti-proliferative activity of some novel 4-aminoquinoline derivatives

Novel nineteen compounds based on a 4-aminoquinoline scaffold were designed and synthesized as potential anti-proliferative agents. The new compounds were N-substituted at the 4-position by aryl or heteroaryl 1-9, quinolin-3-yl 10, 2-methylquinolin-3-yl 11, thiazol-2-yl 12, and dapsone moieties 13, 14 and 18. Bis-compounds 15, 16 and 19 were also synthesized to assess their biological activity. All the newly synthesized comounds were tested for in vitro antiproliferative activity against the MCF-7 breast cancer cell line. Seventeen of the novel compounds showed higher activity than the reference drug doxorubicin. The corresponding 7-(trifluoromethyl)-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine 1, N-(7-(trifluoromethyl)quinolin-4-yl)quinolin-3-amine (10), 2-methyl-N-(7-trifluorome-thyl)quinolin-4-yl)quinolin-3-amine (11) and N-(4-(4-aminophenylsulf-onyl)phenyl)-7-chloroquinolin-4-amine (13) were almost twice to thrice as potent as doxorubicin

Synthesis and biological evaluation of some hybrid 2-quinolinone derivatives containing cinnamic acid as anti-breast cancer drugs

ABSTRACT. A new series of hybrid 2-quinolinone derivatives were synthesized by using 7-hydroxy-4-methyl-1-amino-quinolin-2-one (2) and cinnamic acid. Hybrid halogenated 2-quinolinone derivatives (3-(7-hydroxy-4-methyl-3,6,8-tribromo-2-oxo-2H-quinolin-1-ylamino)-3-phenyl acrylic acid (4) and 3-(7-acetoxy-4-methyl-3,6,8-tribromo-2-oxo-1H-quinolin-1-ylamino)-3-phenyl acrylic acid (7)) were prepared via the halogenation of 3-(7-hydroxy-4-methyl-2-oxo-2H-quinolin-1-ylamino)-3-phenyl acrylic acid (3) with bromine to give compound 4 with acetic anhydride led to the formation of hydride halogenated 2-quinolinone derivative (7). All the synthesized hybrid 2-quinolinone and hybrid halogenated 2-quinolinone derivatives were tested for their cytotoxicity against MCF-7 cell line. DNA flow cytometric analysis of compounds 3 showed cell cycle arrest at G2/M phase with concomitant increase of cells in apoptotic phase. Dual annexin-V/propidium iodide staining assay of compound 3 revealed that, the selected molecule increases the apoptosis of MCF-7 cells more than control.                     KEY WORDS: Quinolinone, Hybrid, Cinnamic acid, Apoptosis, MCF-7 cells   Bull. Chem. Soc. Ethiop. 2021, 35(3), 551-564. DOI: https://dx.doi.org/10.4314/bcse.v35i3.

Green Chemistry and Synthesis of Anticancer Molecule

Green chemistry is a modern area of chemistry merged with chemical engineering methods. It highlighted the synthesis of molecules in a manner of using environment-friendly chemical reagents with low waste material for enhancing environmental performance which reduce the formation of hazard substances. Modern researches are trying to reduce the risk of human kind health and the environment of our world by doing magnificent work in the field of green chemistry. In the pharmaceutical field, green chemistry works very well with the formation of many drugs and it utilizes non-hazards, reproducible and environment-friendly solvents with low time and money costs by using catalyst, microwave, ultrasonic, solid phase and solvent-free synthesis. Until now, scientist has synthesized many anticancer molecules by using these modern green chemistry techniques. These compounds showed significant anticancer activities against many human cancer cell lines. In this chapter, we will cover different views and the recently published literature to summarize the role of green chemistry in the synthesis of anticancer compounds

Novel thiophene derivatives with sulfonamide, isoxazole, benzothiazole, quinoline and anthracene moieties as potential anticancer agents

A novel series of thiophenes having biologically active sulfonamide (2-11), 3-methylisoxazole (12), 4-methoxybenzo[d]thiazole (13), quinoline (14, 15), benzoylphenylamino (16) and anthracene-9,10-dione (17) moieties were prepared. Structures of the newly synthesized compounds were established by elemental analysis and spectral data. All newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Most of the screened compounds showed cytotoxic activities compared to doxorubicin as a positive control. Compounds 6, 7, 9 and 13 (IC50 values 10.25, 9.70, 9.55 and 9.39 µmol L–1 revealed higher cytotoxic activities than that of doxorubicin (IC50 = 32.00 µmol L). Also, compounds 5, 8 and 10 were found nearly as active as doxorubicin (IC50 values 28.85, 23.48 and 27.51 µmol L–1)

Quinoline-based molecules targeting c-Met, EGF, and VEGF receptors and the proteins involved in related carcinogenic pathways

The quinoline ring system has long been known as a versatile nucleus in the design and synthesis of biologically active compounds. Currently, more than one hundred quinoline compounds have been approved in therapy as antimicrobial, local anaesthetic, antipsychotic, and anticancer drugs. In drug discovery, indeed, over the last few years, an increase in the publication of papers and patents about quinoline derivatives possessing antiproliferative properties has been observed. This trend can be justified by the versatility and accessibility of the quinoline scaffold, from which new derivatives can be easily designed and synthesized. Within the numerous quinoline small molecules developed as antiproliferative drugs, this review is focused on compounds effective on c-Met, VEGF (vascular endothelial growth factor), and EGF (epidermal growth factor) receptors, pivotal targets for the activation of important carcinogenic pathways (Ras/Raf/MEK and PI3K/AkT/mTOR). These signalling cascades are closely connected and regulate the survival processes in the cell, such as proliferation, apoptosis, differentiation, and angiogenesis. The antiproliferative biological data of remarkable quinoline compounds have been analysed, confirming the pivotal importance of this ring system in the efficacy of several approved drugs. Furthermore, in view of an SAR (structure-activity relationship) study, the most recurrent ligand–protein interactions of the reviewed molecules are summarized

New arylated benzo[h]quinolines induce anti-cancer activity by oxidative stress-mediated DNA damage

© 2016 The Author(s).The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound. In addition, molecular docking revealed that benzo[h]quinolines can correctly dock into the hydrophobic pocket of the targets receptor protein aromatase and CDK2, while their bioavailability/drug-likeness was predicted to be acceptable but requires future optimization. These findings reveal that benzo[h]quinolines act as anti-cancer agents by inducing oxidative stress-mediated DNA damage

Heterocycles

Heterocycles have constituted the largest area of research in organic chemistry. These heterocycles play an important role in biochemical processes because the side groups of the most typical and essential constituents of living cells, DNA and RNA, are based on aromatic heterocycles. Many synthetic methods have been developed for the preparation of heterocycles. The recent surge of interest in the chemistry of heterocycles can be explained by their unusual properties and exotic structure. These heterocycles include highly stable aromatic compounds that display physicochemical properties with relevance in the design of new materials. Thus, heterocycles contribute to the development of society from a biological and industrial point of view

Synthesis and cytotoxicity evaluation of thiosemicarbazones and their thiazole derivatives

O estudo teve como objetivo a síntese de uma série de tiossemicarbazonas e seus derivados tiazólicos e a avaliação da atividade citotóxica contra três linhagens de células tumorais humanas e células normais (Vero), a fim de se avaliar o potencial pró-apoptótico dos compostos mais ativos. As tiossemicarbazonas foram obtidas por reação entre um aldeído aromático e tiossemicarbazida (rend. 71-96%), as quais foram submetidas à ciclização com α-bromoacetofenona, fornecendo os heterociclos tiazólicos desejados (rend. 63-100%). Todos os compostos sintetizados foram testados na concentração de 50 µM contra três linhagens de células tumorais: HL60 (leucemia promielocítica), Jurkat (leucemia linfoblástica aguda) e MCF-7 (câncer de mama). O efeito pró-apoptótico foi avaliado por citometria de fluxo como porcentagem de células com DNA hipodiplóide. Três compostos tiazólicos foram ativos contra, pelo menos, uma linhagem tumoral (CI50=43-76 µM), com baixa citotoxicidade contra células Vero (CI50 >; 100 M). O composto mais ativo dessa série induziu fragmentação do DNA de 91% e 51% nas linhagens HL60 e MCF-7, respectivamente, sugerindo que este composto ativou a apoptose nessas células. Dentre os compostos sintetizados, um em particular apresentou atividade antiproliferativa e pró-apoptótica em células tumorais e pode ser considerado composto protótipo promissor na busca por novos análogos com atividade melhorada.The aims of this study were to synthesize a series of thiosemicarbazones and their thiazole derivatives, to investigate their cytotoxic activity against three human cancers and normal (Vero cells) cell lines, and to evaluate the pro-apoptotic potential of the most active compounds. Materials and Methods: The thiosemicarbazones were obtained by reacting an aromatic aldehyde with thiosemicarbazide (yield 71-96%), which were subjected to a cyclization with α-bromoacetophenone to yield the required thiazole heterocycles (yield 63-100%). All the synthesized compounds were screened at 50 µM concentration against three cell lines representing HL60 (promyelocytic leukemia), Jurkat (acute lymphoblastic leukemia), and MCF-7 (breast cancer). The pro-apoptotic effect was measured by flow cytometry as the percentage of cells with hypodiploid DNA. Results: Three thiazole compounds showed activity against at least one tumor cell line (IC50 = 43-76 µM) and low cytotoxicity against Vero cells (IC50 >; 100 M). The most active compound of this series induced 91% and 51% DNA fragmentation in HL60 and MCF-7 cell lines, respectively, suggesting that this compound triggered apoptosis in these cells. Conclusion: Among the synthesized compounds, one in particular was found to exert antiproliferative and pro-apoptotic activity on tumor cells and can be considered promising as a lead molecule for the design of new analogues with improved activity

2,4-CYCLOADDITION REACTIONS: PREPARATION AND CYTOTOXICITY OF NOVEL QUINOLINE AND PYRROLO [3,4-f] QUINOLINE DERIVATIVES

Objective: the present work aimed to synthesize novel quinoline and pyrroloquinoline derivatives and study their cytotoxic activity.Methods: Diels–Alder reaction (4+2) was used for the synthesis of new quinolone and pyrrolo quinoline derivatives via the reactions of compound 1 with N-maleimide (4a-d) derivatives, ethyl acrylate (6) methylmethacrylate (8) and acetylene dicarboxylic acid (10). The synthesized compounds were characterized by NMR and Mass spectral data. Some of the synthesized compounds were screened for their antitumor activity against three different cell lines (MCF-7, HepG2 and HCT).Results: The tested compounds exhibited antiproliferative activity against the three different cell lines, especially against MCF-7.Conclusion: New quinoline and pyrroloquinoline derivatives were synthesized starting with 6-methyl-4-phenyl-2-thioxo-5-(4-methylphenylthio)-1,2-dihydropyridine-3-carbonitrile. Two new compounds 3 and 5a were tested for their in vitro antiproliferative activity against MCF-7, HepG2 and HCT cancer cell lines. The result showed that compound 3 exhibited more potent antiproliferative activity than compound 5a in case of MCF-7 and HCT cell lines.Â