Novel Perbutyrylated Glucose Derivatives of (–)-Epigallocatechin-3-Gallate Inhibit Cancer Cells Proliferation by Decreasing Phosphorylation of the EGFR: Synthesis, Cytotoxicity, and Molecular Docking

Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (7–12) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property–activity relationship of EGCG derivatives. Compounds 11 and 12 showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC50 values in the range of 22.90–37.87 μM. Compounds 11 and 12 decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds 11 and 12, both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development.

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Synthesis and Biological Evaluation of matrine derivatives as a Novel Family of Potential Anticancer Agents

Medicinal Chemistry ◽

10.2174/1573406415666191022145534 ◽

2019 ◽

Vol 15 ◽

Author(s):

Jing Wang ◽

Hang Liu ◽

Xiao-Bin Zhuo ◽

Guang-Ming Ye ◽

Qing-Jie Zhao

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Human Cancer ◽

Biological Activities ◽

Parent Compound ◽

Human Tumor ◽

Cancer Cell Lines ◽

Biological Evaluation ◽

Novel Scaffold

Background: ‘FufangKushen injection’ was a Chinese Traditional anticancer drug, which has been widely used to treat cancer in combination with other anticancer drugs. Objective: Our goal is to synthesize a series of novel 13-dithiocarbamates matrine derivatives using matrine (1) as the lead compounnd, and evaluate biological activities of obtained compounds. Method: The in vitro cytotoxicity of the target compounds against three human cancer cell lines (Hep3B, LM3 and BeL-7404) was evaluated. To investigate the mechanism of biological activity, Cell cycle analysis were performed. Result: The results revealed that compound 6o and 6v displayed the most significant anticancer activity against three cancer cell lines with IC50 values in range of 3.42–8.05 μM, which showed better activity than the parent compound (Matrine). SAR analysis indicated that introduction of a substituted amino dithiocarbamate might significantly enhance the antiproliferative activity. Conclusion: During the newly synthesized compounds, matrine analogue 6v exhibited a potent effect against three human tumor cell lines. The mode of action of 6v was to inhibit the G0/G1 phase arrest. Therefore, compound 6v has been selected as a novel-scaffold lead for further structural optimizations or as a chemical probe for exploring anticancer pathways of this kinds of compounds.

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Recent development of tetrahydro-quinoline/isoquinoline based compounds as anticancer agents

Current Topics in Medicinal Chemistry ◽

10.2174/1568026621666210526164208 ◽

2021 ◽

Vol 21 ◽

Author(s):

Pratik Yadav ◽

Ashish Kumar ◽

Ismail Althagafi ◽

Vishal Nemaysh ◽

Reeta Rai ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Human Cancer ◽

Biological Activities ◽

Cancer Cell Lines ◽

New Drugs ◽

Anticancer Activities ◽

Human Cancer Cell Lines ◽

Anticancer Properties

: Tetrahydroquinoline and isoquinoline scaffolds are important class heterocyclic compounds, which is implied for the development of new drugs and diagnostic for therapeutic function. Naturally occurring as well as synthetic tetrahydroquinolines/isoquinolines possess many different biological activities and have been testified as remarkable cytotoxic and potency in human cancer cell lines. Tetrahydroquinoline/isoquinolines based compounds displayed a key role in the development of anticancer drugs or lead molecules and acting through various mechanisms such as cell proliferation, apoptosis, DNA fragmentation, inhibition of tubulin polymerization, induced cell cycle arrest, interruption of cell migration, and modulation. The number of tetrahydroquinoline/isoquinoline derivatives has been reported as potent anticancer agents. Due to promising anticancer activities and wide-ranging properties of these molecules, we have compiled the literature for the synthesis and anticancer properties of various tetrahydroquinolines and isoquinolines. We have reported the synthesis of potent tetrahydroquinoline/isoquinoline molecules of the last 10 years with their anticancer properties in various cancer cell lines and stated their half-maximal inhibitory concentration (IC50). In addition, we also considered the discussion of molecular docking and structural activity relationship wherever provided to understand the possible mode of activity a target involved and structural feature responsible for the better activity, so the reader can directly find the detail for designing new anticancer agents.

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Synthesis and Cytotoxicity Assessment of Novel 7-O- and 14-O-Derivatives of Glaucocalyxin A

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200302114550 ◽

2020 ◽

Vol 20 (10) ◽

pp. 1241-1249

Author(s):

Hong-Chuan Liu ◽

Li-Ming Qiao ◽

Wei Zheng ◽

Zhao-Bao Xiang ◽

Hai-Sheng Chen ◽

...

Keyword(s):

Acute Toxicity ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Folk Medicine ◽

A549 Cells ◽

Cancer Cell Lines ◽

Human Cancer Cell Lines ◽

Derivatives Of

Background: Rabdosia japonica has been historically used in China as a popular folk medicine for the treatment of cancer, hepatitis, and gastricism. Glaucocalyxin A (GLA), an ent-kaurene diterpene isolated from Rabdosia japonica, is one of the main active ingredients showing potent inhibitory effects against several types of tumor cells. To the best of our knowledge, studies regarding the structural modification and Structure- Activity Relations (SAR) of this compound have not yet been reported. Objective: The aim of this study was to discover more potent derivatives of GLA and investigate their SAR and cytotoxicity mechanisms. Methods: Novel 7-O- and 14-O-derivatives of GLA were synthesized by condensation of acids or acyl chloride. The anti-tumor activities of these derivatives against various human cancer cell lines were evaluated in vitro by MTT assays. Apoptosis assays of compound 17 (7,14-diacylation product) were performed on A549 and HL-60 cells by flow cytometry and TUNNEL. The acute toxicity of this compound was tested on mice, at the dose of 300mg per kg body weight. Results: Seventeen novel 7-O- and 14-O-derivatives of GLA (1-17) were synthesized. These compounds showed potent cytotoxicity against the tested cancer cell lines, and almost all of them were found to be more cytotoxic than GLA and oridonin. Of the synthesized derivatives, compound 17 presented the greatest cytotoxicity, with IC50 values of 0.26μM and 1.10μM in HL-60 and CCRF-CEM cells, respectively. Furthermore, this compound induced weak apoptosis of A549 cells but showed great potential in stimulating the apoptosis of HL- 60 cells. Acute toxicity assays indicated that compound 17 is relatively safer. Conclusion: The results reported herein indicate that the synthesized GLA derivatives exhibited greater cytotoxicity against leukemia cells than against other types of tumors. In particular, 7,14-diacylation product of GLA was found to be an effective anti-tumor agent. However, the cytotoxicity mechanism of this product in A549 cells is expected to be different than that in other tumor cell lines. Further research is needed to confirm this hypothesis.

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Synthesis, Antiproliferative activity, and apoptotic profile of New Derivatives from the Meta Stable Benzoxazinone Scaffold

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210706152632 ◽

2021 ◽

Vol 21 ◽

Author(s):

Amira El-Sayed ◽

Maher El-Hashash ◽

Wael El-Sayed

Keyword(s):

Cell Cycle ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Antiproliferative Activity ◽

Human Cancer ◽

Human Fibroblasts ◽

Cancer Cell Lines ◽

Selectivity Index ◽

Human Cancer Cell Lines

Background: Cancer exerts a huge strain on the health system. The emerging resistance to the current chemotherapies demands the continuous development of new anticancer agents with lower cost, higher efficacy, and greater specificity. Objective: Development of selective small molecules targeted anticancer agents Methods: The behavior of benzoxazinone 2 towards nitrogen nucleophiles such as hydrazine hydrate, formamide, ethanolamine, aromatic amines, and thiosemcarbazide was described. The behavior of the amino quinazolinone 3 towards carbon electrophiles and P2S5 was also investigated. The antiproliferative activity of 17 new benzoxazinone derivatives was examined against the growth of three human cancer cell lines; liver HepG2, breast MCF-7, and colon HCT-29, in addition to the normal human fibroblasts WI-38 and the selectivity index was calculated. The possible molecular pathways such as the cell cycle and apoptosis were investigated. Results: Derivatives 3, 7, 8, 10, 13, and 15 had a significant (less than 10 µM) antiproliferative activity against the three cancer cell lines investigated. Derivative 7 showed the best antiproliferative profile comparable to that of doxorubicin. The selectivity index for all the effective derivatives ranged from ~5-12 folds indicating high selectivity against the cancer cells. Derivative 15 caused ~ 7-fold and 8-fold inductions in the expression of p53 and caspase3, respectively. It also caused a ~ 60% reduction in the expression of both topoisomerase II (topoII) and cyclin-dependent kinase 1 (cdk1). Derivatives 3, 7, and 8 had a similar profile; ~ 6-8-fold increases in the expression of p53 and caspase3 but these compounds were devoid of any significant effect on the expression of topoII and cdk1. Derivatives 10 and 13 were also similar and resulted in a ~6-fold elevation in the expression of caspase3, and more than 60% downregulation in the expression of topoII. The results of the gene expression of topoII and caspase 3 were confirmed by the measurement of the topoII concentration and caspase3 activity in the HepG2 cells. Conclusion: Six derivatives exerted their antiproliferative activity by arresting the cell cycle (decreasing cdk1), preventing the DNA duplication (downregulating topo II), and by inducing apoptosis (inducing p53 and caspase3). One common feature in all the six active derivatives is the presence of free amino group. These compounds have merit for further investigations.

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Novel N-bridged pyrazole-1-carbothioamides with potential antiproliferative activity: design, synthesis, in vitro and in silico studies

Future Medicinal Chemistry ◽

10.4155/fmc-2021-0066 ◽

2021 ◽

Vol 13 (20) ◽

pp. 1743-1766

Author(s):

Islam H El Azab ◽

Essa M Saied ◽

Alaa A Osman ◽

Amir E Mehana ◽

Hosam A Saad ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Antiproliferative Activity ◽

In Silico ◽

Human Cancer ◽

Cancer Cell Lines ◽

Molecular Docking Study ◽

In Silico Studies

Thiazole-substituted pyrazole is an important structural feature of many bioactive compounds, including antiviral, antitubercular, analgesic and anticancer agents. Herein we describe an efficient and facile approach for the synthesis of two series of 36 novel N-bridged pyrazole-1-phenylthiazoles. The antiproliferative activity of a set of representative compounds was evaluated in vitro against different human cancer cell lines. Among the identified compounds, compound 18 showed potent anticancer activity against the examined cancer cell lines. The in silico molecular docking study revealed that compound 18 possesses high binding affinity toward both SK1 and CDK2. Overall, these results indicate that compound 18 is a promising lead anticancer compound which may be exploited for development of antiproliferative drugs.

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

Canadian Journal of Chemistry ◽

10.1139/cjc-2013-0053 ◽

2013 ◽

Vol 91 (8) ◽

pp. 741-754 ◽

Cited By ~ 9

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.

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Pharmacological Evaluation of the Anticancer Activity of Extracts and Fractions of Lannea barteri Oliv. (Anacardiaceae) on Adherent Human Cancer Cell Lines

Molecules ◽

10.3390/molecules25040849 ◽

2020 ◽

Vol 25 (4) ◽

pp. 849 ◽

Cited By ~ 1

Author(s):

Florence N. Mbaoji ◽

Steven Behnisch-Cornwell ◽

Adaobi C. Ezike ◽

Chukwuemeka S. Nworu ◽

Patrick J. Bednarski

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Human Cancer ◽

Stem Bark ◽

Cancer Cell Lines ◽

Human Carcinoma ◽

Human Cancer Cell Lines ◽

Western Africa

In western Africa ethnomedicine, Lannea barteri Oliv. (Anacardiaceae) is believed to have activity against gastrointestinal, neurological and endocrine diseases. Previous studies on this plant have revealed antimicrobial, anticholinestrase, anticonvulsant, antioxidant and anti-inflammatory activities. However, the anticancer potential of L. barteri has not been studied to date. The aim of this study was to evaluate the anticancer potential of hot and cold extracts and silica gel column chromatographic fractions of L. barteri leaf and stem bark. The extracts and fractions were tested for anticancer activity by using the crystal violet cell proliferation assay on four adherent human carcinoma cell lines—5637 (bladder), KYSE 70 (oesophagus), SiSo (cervical) and HepG2 (hepatic). The inhibitory concentration (IC50) of fractions IH, 1I, 2E and 2F were: 3.75 ± 1.33, 3.88 ± 2.15, 0.53 ± 0.41, and 0.42 ± 0.45 µg/mL against KYSE 70 and 1.04 ± 0.94, 2.69 ± 1.17, 2.38 ± 3.64, 2.17 ± 1.92 µg/mL against SiSo cell lines respectively. Fraction 2E showed weak apoptotic activity at double the IC50 and some sign of cell cycle arrest in the G2/M phase. Thus, phytoconstituents of L. barteri leaf and stem bark can inhibit the proliferation of cancer cell lines indicating the presence of possible anticancer agents in this plant.

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Design and Evaluation of Licochalcone A Derivatives as Anticancer Agents

Natural Product Communications ◽

10.1177/1934578x1801300609 ◽

2018 ◽

Vol 13 (6) ◽

pp. 1934578X1801300

Author(s):

Goo Yoon ◽

Seung Hoon Cheon ◽

Jung Hyun Shim ◽

Seung Sik Cho

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Cancer Cell Lines ◽

Anticancer Activities ◽

Licochalcone A ◽

Lead Compounds ◽

Further Development ◽

Derivatives Of

New derivatives of licochalcone A were synthesized and evaluated for their potential anticancer activities. Compounds 6 (( E)-N-(4-(3-(5-bromo-4-hydroxy-2-methoxy phenyl) acryloyl) phenyl)-4-isopropylbenzamide) and 8 (1-(3-dimethylamino-phenyl)-3-(2-trifluoromethyl-phenyl)-propenone) showed potent activity against the screened cancer cell lines with that of compound 6 ranging from 6.9 ± 0.2 μM to 22.9 ± 3.1 μM, and that of compound 8 from 4.2 ± 0.5 μM to 11.8 ± 0.7 μM. Both compounds showed stronger cytotoxicity than that of licochalcone A. These two candidates have very different substituents and could be considered as promising lead compounds for further development of potent anticancer agents.

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