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.

Novel Conjugated Quinazolinone-Based Hydroxamic Acids: Design, Synthesis and Biological Evaluation

2020 ◽  
Vol 16 ◽  
Author(s):  
Tran Khac Vu ◽  
Nguyen Thi Thanh ◽  
Nguyen Van Minh ◽  
Nguyen Huong Linh ◽  
Nguyen Thi Phương Thao ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Cell Lines ◽  
Cancer Cell ◽  
Hdac Inhibitors ◽  
Cancer Cell Lines ◽  
Hydroxamic Acids ◽  
Biological Evaluation ◽  
Hdac Inhibition ◽  
Ic50 Value ◽  
Mcf 7

Background: Target-based approach to drug discovery currently attracts a great deal of interest from medicinal chemists in anticancer drug discovery and development. Histone deacetylase (HDAC) inhibitors represent an extensive class of targeted anti-cancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as vorinostat and belinostat. Aims: This study aims at developing novel HDAC inhibitors bearing conjugated quinazolinone scaffolds with potential cytotoxicity against different cancer cell lines. Method: A series of novel N-hydroxyheptanamides incorporating conjugated 6-hydroxy-2 methylquinazolin-4(3H)- ones (15a-l) was designed, synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines, including HepG-2, MCF-7 and SKLu-1. Molecular simulations were finally performed to gain more insight into the structure-activity. relationships. Results: It was found that among novel conjugated quinazolinone-based hydroxamic acids synthesized, compounds 15a, 15c and 15f were the most potent, both in terms of HDAC inhibition and cytotoxicity. Especially, compound 15f displayed up to nearly 4-fold more potent than SAHA (vorinostat) in terms of cytotoxicity against MCF-7 cell line with IC50 value of 1.86 µM, and HDAC inhibition with IC50 value of 6.36 µM. Docking experiments on HDAC2 isozyme showed that these compounds bound to HDAC2 with binding affinities ranging from -10.08 to -14.93 kcal/mol compared to SAHA (-15.84 kcal/mol). It was also found in this research that most of the target compounds seemed to be more cytotoxic toward SKLu-1than MCF-7 and HepG-2. Conclusion: The resesrch results suggest that some hydroxamic acids could emerge for further evaluation and the results are well served as basics for further design of more potent HDAC inhibitors and antitumor agents.

In Vitro Antitumor Evaluation of Some Hybrid Molecules Containing Coumarin and Quinolinone Moieties

2020 ◽  
Vol 19 (16) ◽  
pp. 2010-2018
Author(s):  
Youstina W. Rizzk ◽  
Ibrahim M. El-Deen ◽  
Faten Z. Mohammed ◽  
Moustafa S. Abdelhamid ◽  
Amgad I.M. Khedr
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Cancer Cell Lines ◽  
Bax Protein ◽  
Hybrid Molecules ◽  
Mcf 7

Background: Hybrid molecules furnished by merging two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery. Currently, coumarin hybrids have attracted the keen attention of researchers to discover their therapeutic capability against cancer. Objective: The present study aimed to evaluate the in vitro antitumor activity of a new series of hybrid molecules containing coumarin and quinolinone moieties 4 and 5 against four cancer cell lines. Materials and Methods: A new series of hybrid molecules containing coumarin and quinolinone moieties, 4a-c and 5a-c, were synthesized and screened for their cytotoxicity against prostate PC-3, breast MCF-7, colon HCT- 116 and liver HepG2 cancer cell lines as well as normal breast Hs-371 T. Results: All the synthesized compounds were assessed for their in vitro antiproliferative activity against four cancer cell lines and several compounds were found to be active. Further in vitro cell cycle study of compounds 4a and 5a revealed MCF-7 cells arrest at G2 /M phase of the cell cycle profile and induction apoptosis at pre-G1 phase. The apoptosis-inducing activity was evidenced by up-regulation of Bax protein together with the downregulation of the expression of Bcl-2 protein. The mechanism of cytotoxic activity of compounds 4a and 5a correlated to its topoisomerase II inhibitory activity. Conclusion: Hybrid molecules containing coumarin and quinolinone moieties represents a scaffold for further optimization to obtain promising anticancer agents.

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.

Anticancer and antioxidant studies of the methanol extract and fractions of Conyza sumatrensis (retz.) E. H. Walker (asteraceae

2020 ◽  
Vol 23 ◽  
pp. 77-82
Author(s):  
E.O. Ikpefan ◽  
B.A. Ayinde ◽  
B.A. Mudassar ◽  
Ahsana Dar Farooq
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Antioxidant Activities ◽  
Cancer Cell Lines ◽  
Total Phenolic ◽  
Chloroform Fraction ◽  
Aqueous Fraction ◽  
Growth Inhibitory ◽  
Mcf 7

The in vitro antiproliferative and antioxidant studies of the leaf extract and fractions of Conyza sumatrensis was investigated by applying the Sulforhodamine-B and 2, 2-diphenyl-1-picrylhydrazyl assays (DPPH-RSA) respectively. While the antiproliferative activity was carried out at 1-250 and 1-100 μg/ mL for the extract and fractions against breast (MCF-7) and lung (NCI-H460) cancer cell lines, the antioxidant study was conducted using DPPH at 31.25 -500 μg/ mL with the total phenolic and flavonoid contents calculated as well with reference to quercetin and gallic acid respectively. The extract and fractions were observed to elicit cytotoxic and growth inhibitory effects against breast (MCF-7) and lung cancer cell lines (NCI-H460) respectively. At 250 μg/mL, the extract of C. sumatrensis gave cytotoxicity of –1.76 ± 0.20 % against MCF-7 cell lines and inhibited growth of NCI-H460 at +94.40 ± 1.0 % respectively. While the chloroform fraction at 100 μg/mL gave -5.38 ± 0.33 % and 91 ± 1.61 % against MCF-7 and NCI-H460 cell lines, the aqueous fraction was observed to be inactive. For the DPPH-RSA activity, the chloroform fraction demonstrated an IC50 value of 125.5 μg/ mL compare to quercetin at 62.5 μg/ mL. The bioactivities were more pronounced in the chloroform fraction. This work has shown that C.  sumatrensis has antiproliferative and antioxidant activities which could be tied to the secondary metabolites present in the plant.

The In Vitro Anticancer Activity and Potential Mechanism of Action of 1-[(1R,2S)-2-fluorocyclopropyl]Ciprofloxacin-(4-methyl/phenyl/benzyl-3- aryl)-1,2,4-triazole-5(4H)-thione Hybrids

2020 ◽  
Vol 20 (16) ◽  
pp. 1493-1498
Author(s):  
Ya-Zhou Zhang ◽  
Hai-Lin Liu ◽  
Qian-Song He ◽  
Zhi Xu
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Drug Resistant ◽  
Mcf 7

Aims: Development of 1-[(1R, 2S)-2-fluorocyclopropyl]ciprofloxacin-1,2,4-triazole-5(4H)- thione hybrids as potential dual-acting mechanism anticancer agent to overcome the drug resistance. Background: Chemotherapy is an essential tool for the treatment of lung and female breast cancers, and numerous anticancer agents have been launched for this purpose. However, the clinical outcomes of chemotherapy are usually far from satisfactory due to the side effects and resistance to chemotherapeutic drugs. Thus, it is urgent to develop novel anti-lung and anti-breast cancer agents. Background: Chemotherapy is an essential tool for the treatment of lung and female breast cancers, and numerous anticancer agents have been launched for this purpose. However, the clinical outcomes of chemotherapy are usually far from satisfactory due to the side effects and resistance to chemotherapeutic drugs. Thus, it is urgent to develop novel anti-lung and anti-breast cancer agents. Objective: The primary objective of this study was to evaluate the potential of bis-isatin scaffolds with alkyl/ether linkers between the two isatin moieties against different human breast cancer cell lines including A549, MCF-7 and their drug-resistant counterparts A549/CDDP, MCF-7/ADM cells. Methods: The 1-[(1R, 2S)-2-fluorocyclopropyl]ciprofloxacin-(4-methyl/phenyl/benzyl-3-aryl)-1,2,4- triazole-5(4H)-thione hybrids were screened for their in vitro activity against drug-sensitive lung (A549), breast (MCF-7) and their drug-resistant counterparts A549/CDDP (cisplatin-resistant), MCF- 7/ADM (doxorubicin-resistant) cancer cell lines by MTT assay. The inhibitory activity of these hybrids against topoisomerase II and EGFR was also evaluated to investigate the potential mechanism of action of these hybrids. Result: The most prominent hybrid 7k (IC50: 37.28-49.05 µM) was comparable to Vorinostat against A549 and A549/CDDP lung cancer cells, and was 2.79-2.94 times more active than Vorinostat against MCF-7 and MCF-7/ADM breast cancer cell lines. Moreover, hybrid 7k (IC50: 8.6 and 16.4 µM) also demonstrated dual inhibition against topoisomerase II and EGFR. Conclusion: The 1-[(1R, 2S)-2-fluorocyclopropyl]ciprofloxacin-1,2,4-triazole-5(4H)-thione hybrids possess equally activity against both drug-sensitive cancer cells and their drug-resistant counterparts, and the majority of them were no inferior to the reference Vorinostat. The mechanistic study revealed that these hybrids could inhibit both topoisomerase II and EGFR, so these hybrids can be developed as dual-acting mechanism anticancer agents.

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 Isolation and Cytotoxic Activity of Phyllocladanes from the Roots of Acacia schaffneri (Leguminosae)

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3944
Author(s):  
José de Jesús Manríquez-Torres ◽  
Marco Antonio Hernández-Lepe ◽  
José Román Chávez-Méndez ◽  
Susana González-Reyes ◽  
Idanya Rubí Serafín-Higuera ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Spectroscopic Properties ◽  
Cancer Cell Lines ◽  
Moderate Activity ◽  
Cycle Arrest ◽  
Ic50 Values

In research on natural molecules with cytotoxic activity that can be used for the development of new anticancer agents, the cytotoxic activity of hexane, chloroform, and methanol extracts from the roots of Acacia schaffneri against colon, lung, and skin cancer cell lines was explored. The hexane extract showed the best activity with an average IC50 of 10.6 µg mL−1. From this extract, three diterpenoids, phyllocladan-16α,19-diol (1), phyllocladan-16α-ol (2), and phylloclad-16-en-3-ol (3), were isolated and characterized by their physical and spectroscopic properties. Diterpenoids 1 and 2 were tested against the same cancer cell lines, as well as their healthy counterparts, CCD841 CoN, MRC5, and VH10, respectively. Compound 1 showed moderate activity (IC50 values between 24 and 70 μg mL−1), although it showed a selective effect against cancer cell lines. Compound 2 was practically inactive. The cytotoxicity mechanism of 1 was analyzed by cell cycle, indicating that the compound induces G0/G1 cell cycle arrest. This effect might be generated by DNA alkylation damage. In addition, compound 1 decreased migration of HT29 cells.

Synthesis and biological evaluation of bivalent β-carbolines as potential anticancer agents

MedChemComm ◽  
2016 ◽  
Vol 7 (4) ◽  
pp. 636-645 ◽  
Author(s):  
Hongtao Du ◽  
Hongling Gu ◽  
Na Li ◽  
Junru Wang
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Apoptosis Induction ◽  
Synthesis And Biological Evaluation

A series of novel bivalent β-carbolines were synthesized and evaluated for their anti-proliferative activities on a panel of cancer cell lines, apoptosis induction and cell cycle effects.

scholarly journals Physicochemical Composition, Antioxidant Profile and Anticancer Potentialities of Chico (Pachycereus Weberi) and Jiotilla (Escontria Chiotilla) Fruits Extract

2020 ◽  
Author(s):  
Luisaldo Sandate-Flores ◽  
Eduardo Romero-Esquivel ◽  
Patricia Reyna Ontiveros ◽  
Marcos Fredy Morales Celaya ◽  
José Rodriguez-Rodriguez ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Vitamin C ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Biologically Active ◽  
Normal Fibroblast ◽  
Total Phenolic ◽  
Escontria Chiotilla ◽  
Mcf 7

Mexico has a great diversity of cacti, however, many of their fruits have not been studied in greater depth. Several bioactive compounds available in cacti juices extract have demonstrated nutraceutical properties. Two cactus species are interesting for their biologically active pigments, which are chico (Pachycereus weberi (J. M.Coult.) Backeb)) and jiotilla (Escontria chiotilla (Weber) Rose)). Hence, the goal of this work was to evaluate the bioactive entities, i.e., betalains, total phenolic, vitamin C, antioxidant activity, and mineral content in the extract of the above-mentioned P. weberi and E. chiotilla. Then, clarified extracts were evaluated for their antioxidant activity and cytotoxicity (cancer cell lines) potentialities. Based on the obtained results, Chico fruit extract was found to be a good source of vitamin C (27.19±1.95 mg L-Ascorbic acid/100g fresh sample). Moreover, chico extract resulted in a high concentration of micronutrients, i.e., potassium (517.75±16.78 mg/100 g) and zinc (2.46±0.65 mg/100 g). On the other hand, Jiotilla has a high content of biologically active pigment, i.e., betaxanthins (4.17±0.35 mg/g dry sample). The antioxidant activities of clarified extracts of chico and jiotilla were 80.01±5.10 and 280.88±7.62 (DPPH method), respectively. From the cytotoxicity perspective against cancer cell lines, i.e., CaCo-2, MCF-7, HepG2, and PC-3, the clarified extracts of chico showed cytotoxicity in CaCo-2 (49.7±0.01) and MCF-7 (45.56±0.05). Normal fibroblast cell line (NIH/3T3) was used as a control for comparison purposes. While, jiotilla extract had cytotoxicity against HepG2 (47.31±0.03) and PC-3 (53.65±0.04). These results demonstrated that Chico and jiotilla are good resources of biologically active constituents with nutraceuticals potentialities.

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.

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