scholarly journals Synthesis and Biological Evaluation of Harmirins, Novel Harmine–Coumarin Hybrids as Potential Anticancer Agents

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6490
Author(s):  
Kristina Pavić ◽  
Maja Beus ◽  
Goran Poje ◽  
Lidija Uzelac ◽  
Marijeta Kralj ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Hct116 Cell ◽  
Biological Evaluation ◽  
G1 Arrest ◽  
Single Digit ◽  
Mcf 7

As cancer remains one of the major health burdens worldwide, novel agents, due to the development of resistance, are needed. In this work, we designed and synthesized harmirins, which are hybrid compounds comprising harmine and coumarin scaffolds, evaluated their antiproliferative activity, and conducted cell localization and cell cycle analysis experiments. Harmirins were prepared from the corresponding alkynes and azides under mild reaction conditions using Cu(I) catalyzed azide–alkyne cycloaddition, leading to the formation of the 1H-1,2,3-triazole ring. Antiproliferative activity of harmirins was evaluated in vitro against four human cancer cell lines (MCF-7, HCT116, SW620, and HepG2) and one human non-cancer cell line (HEK293T). The most pronounced activities were exerted against MCF-7 and HCT116 cell lines (IC50 in the single-digit micromolar range), while the most selective harmirins were 5b and 12b, substituted at C-3 and O-7 of the β-carboline core and bearing methyl substituent at position 6 of the coumarin ring (SIs > 7.2). Further experiments demonstrated that harmirin 12b is localized exclusively in the cytoplasm. In addition, it induced a strong G1 arrest and reduced the percentage of cells in the S phase, suggesting that it might exert its antiproliferative activity through inhibition of DNA synthesis, rather than DNA damage. In conclusion, harmirin 12b is a novel harmine and coumarin hybrid with significant antiproliferative activity and warrants further evaluation as a potential anticancer agent.

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

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.

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

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.

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.

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

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.

scholarly journals Antiproliferative, antimicrobial, and antioxidant activity of Lavandula angustifolia Mill. essential oil

2017 ◽  
Vol 7 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Haris Niksic ◽  
Elvira Kovac-Besovic ◽  
Elma Omeragic ◽  
Samija Muratovic ◽  
Jasna Kusturica ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Essential Oil ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Gas Chromatography Mass Spectrometry ◽  
Lavandula Angustifolia ◽  
Mcf 7

Introduction: We studied the chemical composition and antimicrobial, antioxidant, and antiproliferative activities of essential oils from flowers of Lavandula angustifolia grown in Southern Bosnia and Herzegovina. Methods: The chemical profile of essential oil was evaluated by means of gas chromatography-mass spectrometry. Antimicrobial activity was tested against six bacterial strains. The antioxidant activity by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) test and the antiproliferative activity against three human cancer cell lines, MCF-7, NCI-H460, and MOLT-4, were investigated using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide tests. Results: In L. angustifolia essential oil, monoterpene alcohols were the most represented class of volatiles (51.8%), including linalool, lavandulol, and terpinen-4-ol, α-terpineol as the major components, followed by monoterpene esters (22.6%). The most important antibacterial activity of essential oil was expressed on Gram-negative strains. Investigated essential oil was able to reduce DPPH radicals into the neutral DPPH-H form (inhibitory concentration 50% [IC50] = 0.421 mg/ml), and this activity was dose dependent. The essential oil showed significant antiproliferative activity against three cancer cell lines, MOLT-4, MCF-7, and NCI-H460 cells, with IC50 values of 17, 94, and 97 µg/ml, respectively. The result of the antiproliferative assay indicates that MOLT-4 cell line was the most sensitive to investigated essential oil. Conclusion: The results revealed that L. angustifolia essential oil may be important growth inhibitor against the microbes studied. It also possesses significant antioxidant activity and demonstrated excellent antiproliferative activity against MOLT-4 cells.

scholarly journals INHIBITORY ACTIVITIES OF CAMELLIA MISTLETOE (K. JAPONICA) EXTRACTS ON PANCREATIC LIPASE, TYROSINASE AND CANCER CELL PROLIFERATION

2017 ◽  
Vol 9 (10) ◽  
pp. 187
Author(s):  
Min Young Kim
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Lipase ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Mistletoe Extracts ◽  
Inhibitory Activities ◽  
Lipase Inhibition

Objective: The objective of this study was undertaken to examine pancreatic lipase and tyrosinase inhibitory activities of Camellia mistletoe (Korthalsella japonica) extracts and conduct their antiproliferative activity on several human cancer (Hela, A375, HCT 116, HepG2 and A549) and normal cells (TK6) lines.Methods: The lipase inhibitory activity of acts of Camellia mistletoe extracts were determined from the hydrolytic reaction of p-nitrophenyl butyrate with pancreatic lipase and cytotoxicity against human cancer and normal cell lines were also evaluated using the MTT assay. The in vitro tyrosinase inhibitor potency of Camellia mistletoe extracts was estimated using mushroom tyrosinase.Results: Both methanol and ethanol extracts of Camellia mistletoe exhibited an inhibitory effect on lipase inhibition activity with IC50 values of 0.39 and 0.49 mg/ml, respectively. Moreover, Camellia mistletoe extracts were judged to be strongly active against the cancer cell lines, while they had no antiproliferative activity against the normal human cell lines. However, they had little inhibitory effects on tyrosinase activity.Conclusion: Camellia mistletoe extracts could be the good sources of natural lipase inhibition and anticancer agents with a great potential to be used in food and therapeutic fields.

Synthesis of (Z)-(arylamino)-pyrazolyl/isoxazolyl-2-propenones as tubulin targeting anticancer agents and apoptotic inducers

2015 ◽  
Vol 13 (11) ◽  
pp. 3416-3431 ◽  
Author(s):  
Ahmed Kamal ◽  
Vangala Santhosh Reddy ◽  
Anver Basha Shaik ◽  
G. Bharath Kumar ◽  
M. V. P. S. Vishnuvardhan ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Tubulin Polymerization ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
New Class

A new class of pyrazole conjugates were synthesized and evaluated for their antiproliferative activity in human cancer cell lines: 9a, 9b and 9f significantly inhibited cell growth as well as tubulin polymerization.

scholarly journals Design, synthesis, and biological evaluation of phenyl-isoxazole-carboxamide derivatives as anticancer agents

2021 ◽  
Vol 27 (1) ◽  
pp. 133-141
Author(s):  
Mohammed Hawash ◽  
Nidal Jaradat ◽  
Noor Bawwab ◽  
Kamilah Salem ◽  
Hadeel Arafat ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Antioxidant Activities ◽  
Dose Range ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Moderate Activity ◽  
Mcf 7

Abstract The present study aimed to design and synthesize a series of phenyl-isoxazole-carboxamide derivatives and investigate their antitumor and antioxidant activities. The in vitro cytotoxic evaluation was conducted using the MTS assay against four cancer cell lines: hepatocellular carcinoma (Hep3B and HepG2), cervical adenocarcinoma (HeLa), breast carcinoma (MCF-7), in addition to the normal cell line (Hek293T). Besides, the antioxidant activity was evaluated using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. All obtained compounds were found to have potent to moderate activities against Hep3B and MCF-7 cancer cells lines, except compound 2e. It was found that compound 2a has potent activity against HeLa and Hep3B cancer cell lines with IC50 values of 0.91 and 8.02 µM, respectively. The IC50 dose range of the tested compounds against Hep3B was 5.96–28.62 µM, except for 2e, compared with doxorubicin, which has an IC50 value of 2.23 µM. Also, the IC50 value range of the compounds against Hek293T was 112.78–266.66 µM, compared with doxorubicin, which has an IC50 dose of 0.581 µM. The antioxidant activity of the synthesized compounds was weak, and compound 2d showed moderate activity against the DPPH enzyme with an IC50 value of 138.50 µM in comparison with Trolox, which has an IC50 dose of 37.23 µM.

Antiproliferative Activity and Characterization of Metabolites of Aspergillus nidulans: An Endophytic Fungus from Nyctanthes arbor-tristis Linn. Against Three Human Cancer Cell Lines

2019 ◽  
Vol 15 (4) ◽  
pp. 352-359 ◽  
Author(s):  
Talea Sana ◽  
Bina S. Siddiqui ◽  
Saleem Shahzad ◽  
Ahsana D. Farooq ◽  
Faheema Siddiqui ◽  
...  
Keyword(s):  
Aspergillus Nidulans ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Endophytic Fungus ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Mcf 7

Background: Endophytic fungi are receiving attention as sources of structurally novel bioactive secondary metabolites towards drug discovery from natural products. This study reports the isolation and characterization of secondary metabolites from an endophytic fungus Aspergillus nidulans, associated with Nyctanthes arbor-tristis Linn., a plant which has a traditional use to cure many ailments including cancer. Objective: The objective of this study was to evaluate the antiproliferative activity of the metabolites of A. nidulans from N. arbor-tristis on three human cancer cell lines, lung (NCI-H460), breast (MCF-7) and uterine cervix (HeLa), and carry out their characterization. Methods: The extracts of the endophytic fungus cultured on potato dextrose agar were subjected to various chromatographic techniques. Structures of pure compounds were determined using spectroscopic techniques. The non-polar constituents were analyzed by GC-MS. Antiproliferative activity was determined by sulforhodamine B (SRB) assay. Results: The extracts and fractions showed moderate to good growth inhibition of the aforementioned human cancer cell lines. The broth extract was most potent (IC50 = 10 ± 3.1 μg/mL and LC50= 95 ± 3.9) against HeLa whereas petroleum ether insoluble fraction of mycelium was most active against NCI-H460 and MCF-7 (IC50 = 10 ± 2.1 µg/mL and 18 ± 3.1 µg/mL respectively). GC-MS led to identify 12 compounds in mycelium and 19 compounds in broth. Four pure compounds were isolated and characterized one compound 5, 10-dihydrophenazine-1-carboxylic acid (1) from broth and three 1-hydroxy-3-methylxanthone (2), ergosterol (3) and sterigmatocystin (4) from mycelium. 1 has not been reported earlier as a plant/fungal metabolite while 2-4 are new from this source. Sterigmatocystin exhibited growth inhibitory effect (IC50 = 50 ± 2.5 µM/mL) against only MCF-7 cell line whereas other compounds had IC50 > 100. Conclusions: In this paper, the cytotoxicity of mycelium and broth constituents of endophytic fungus Aspergillus nidulans from Nyctanthes arbor-tristis is reported for the first time. The study shows that fungus Aspergillus nidulans from Nyctanthes arbor-tristis is capable of producing biologically active natural compounds and provides a scientific rationale for further chemical investigations of endophyte-producing natural products.

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