Synthesis and Characterization of New Series of 1,3-5-Triazine Hydrazone Derivatives with Promising Antiproliferative Activity

A new series of s-triazine hydrazone derivatives was prepared based on the reaction of 6-hydrazino-2,4-disubstituted-s-triazine with p-substituted benzaldehyde derivatives using a straightforward synthetic pathway. The antiproliferative activity of all synthesized compounds was evaluated against two human cancer cell lines; breast cancer MCF-7 and colon carcinoma HCT-116 using MTT assay. Among all, 11 compounds have shown strong to moderate antiproliferative activity with IC50 values in the range 1.01–18.20 µM in MCF-7 and 0.97–19.51 µM in HCT-116. The best results were obtained with 4,4’-(6-(2-(pyridin-2-ylmethylene)hydrazinyl)-1,3,5-triazine-2,4-diyl) dimorpholine 11 (IC50 = 1.0 µM and 0.98 µM in MCF-7 and HCT-116 cell lines, respectively). The substituents on the s-triazine core as well as the substituent at the benzylidene moiety have a great effect on the antiproliferative activity. Whereas compounds containing dimorpholino-s-triazine derivatives 8a–e showed more potent antiproliferative in MCF-7 compared to their analogs 7a–f (compounds containing two-piperidine rings), compounds containing one piperidine and one morpholine ring 9a–f showed better IC50 values in the range 10.4–22.2 µM. On the other hand, compounds containing two-piperidine rings 7a–f showed more potent antiproliferative in HCT-116 (IC50 values in the range 8.8–19.5 µM) than their analogs 8a–e and 9a–f.

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Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

Molecules ◽

10.3390/molecules26133923 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3923

Author(s):

Adel A.-H. Abdel-Rahman ◽

Amira K. F. Shaban ◽

Ibrahim F. Nassar ◽

Dina S. EL-Kady ◽

Nasser S. M. Ismail ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Molecular Docking Study ◽

Human Cancer Cell Lines ◽

Hct 116 ◽

Mcf 7

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

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Four New ent-Kaurane Diterpene Glycosides from Isodon henryi

Molecules ◽

10.3390/molecules24152736 ◽

2019 ◽

Vol 24 (15) ◽

pp. 2736 ◽

Cited By ~ 4

Author(s):

Liu ◽

Zhang ◽

Wu ◽

Chen ◽

Li ◽

...

Keyword(s):

Cell Lines ◽

Human Cancer ◽

Spectroscopic Methods ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Aerial Parts ◽

Ic50 Values ◽

Hct 116 ◽

Relationship Of ◽

First Time

To obtain diterpene glycosides from an aqueous extract of the aerial parts of Isodon henryi and further investigate their cytotoxicities, in this study, a total of seven compounds were isolated, including six ent-kaurane diterpene glycosides (1–6) and one diterpene aglycon (7). Among the seven ent-kaurane diterpenes obtained, four were novel compounds, including ent-7,20-epoxy- kaur-16-en-1α,6β,7β,15β-tetrahydroxyl-11-O-β-d-glucopyranoside (1), ent-7,20-epoxy-kaur-16-en- 6β,7β,14β,15β-tetrahydroxyl-1-O-β-d-glucopyranoside (2), ent-7,20-epoxy-kaur-16-en-6β,7β,15β- trihydroxyl-1-O-β-d-glucopyranoside (3), and ent-7,20-epoxy-kaur-16-en-7β,11β,14α,15β-tetrahydr- oxyl-6-O-β-d-glucopyranoside (4), and three were isolated from this plant for the first time (5–7). Their structures were elucidated by utilizing spectroscopic methods and electronic circular dichroism analyses. Furthermore, the cytotoxicities of all seven compounds were investigated in four human cancer cell lines, including A2780, BGC-823, HCT-116, and HepG2. The IC50 values of these diterpenes ranged from 0.18 to 2.44 mM in the tested cell lines. In addition, the structure–cytotoxicity relationship of diterpene glycosides was also evaluated to study the effect of glycosylation on the cytotoxicity of diterpene compounds.

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Two New Cytotoxic Steroidal Alkaloids from Sarcococca Hookeriana

Molecules ◽

10.3390/molecules24010011 ◽

2018 ◽

Vol 24 (1) ◽

pp. 11 ◽

Cited By ~ 1

Author(s):

Shaojie Huo ◽

Jichun Wu ◽

Xicheng He ◽

Lutai Pan ◽

Jiang Du

Keyword(s):

Cell Lines ◽

Human Cancer ◽

Cytotoxic Activities ◽

Steroidal Alkaloids ◽

X Ray ◽

Human Cancer Cell Lines ◽

X Ray Crystallography ◽

Ic50 Values ◽

Mcf 7

Two new steroidal alkaloids, named hookerianine A (1) and hookerianine B (2) were isolated from the stems and roots of Sarcococca hookeriana Baill., along with two known compounds, sarcorucinine G (3) and epipachysamine D (4). On the basis of spectroscopic methods and by comparison with literature data, their structures were determined. As well as X-ray crystallography was performed to confirm compound 4. To identify novel antitumor inhibitors, all compounds were performed a CCK-8 assay against five human cancer cell lines SW480, SMMC-7721, PC3, MCF-7 and K562 in vitro. Compound 2 exhibited moderate cytotoxic activities to all cell lines with IC50 values in the range of 5.97–19.44 μM. Compound 3 was the most effective one against SW480 and K562 cell lines with IC50 values of 5.77 and 6.29 μM, respectively.

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Novel Artemisinin-Derived Dimers: Synthesis and Evaluation of Anti-cancer Activities

Letters in Drug Design & Discovery ◽

10.2174/1570180813666160810155354 ◽

2016 ◽

Vol 14 (1) ◽

pp. 102-111 ◽

Cited By ~ 4

Author(s):

Vu Tuan Kien ◽

Le Huy Binh ◽

Phan Hai Phong ◽

Doan Thi Hien ◽

Nguyen Thi Thuy My ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Anticancer Compounds ◽

Human Cancer Cell Lines ◽

Ic50 Values ◽

Mcf 7

In continuation of our study on anticancer compounds, a series of novel artemisinin dimers have been synthesized and evaluated for their cytotoxic effects against three human cancer cell lines, including HepG2 (liver cancer), MCF-7(breast cancer) and HL-60 (leukemia cancer). The assay results showed that most of the compounds displayed inhibitory effects against all three human cancer cell lines tested, and seemed to be more cytotoxic toward the blood cancer cells (HL-60) than liver (HepG2), and breast (MCF-7) cancer cells. Among the synthesized artemisinin dimers, the compound 10d with a double bond bridge exhibited the most potent cytotoxicity with IC50 values of 5.08, 4.82 and 1.32 µg/mL against the HepG2, MCF-7, and HL-60 cell lines, respectively.

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Synthesis of New Zerumbone Hydrazones and Their In vitro Anticancer Activity

Current Bioactive Compounds ◽

10.2174/1573407216999200630133625 ◽

2020 ◽

Vol 16 ◽

Author(s):

Vu Van Vu ◽

Tran Khac Vu

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Cytotoxic Effects ◽

Human Cancer Cell Lines ◽

Ic50 Values ◽

Bioassay Result ◽

Mcf 7

Background: A series of new zerumbone hydrazones 5a-f and 9a-f have been synthesized via an in situ procedure in high yields. The structure of synthesized compounds has been confirmed using 1H, 13C NMR and HR-MS. The bioassay result showed that several compounds exhibited cytotoxic effects against three human cancer cell lines including HepG-2, SK-LU-1 and MCF-7. Compound 9a showed the best cytotoxic effect against HepG-2, SK-LU-1 and MCF-7 with IC50 values of 8.20, 6.66 and 9.35 µM, respectively. Objective: This study aims at developing new zerumbone hydrazones as anticancer agents based on zerumbone, a natural compound wildly growing in Vietnam. Method: A series of new zerumbone hydrazones was designed, synthesized and evaluated for cytotoxicity against three human cancer cell lines, including HepG-2, MCF-7 and SKLu-1 using MTT method. Results: The bioassay result showed that several compounds exhibited cytotoxic effects against three human cancer cell lines including HepG-2, SK-LU-1 and MCF-7. Especially, compound 9a displayed the best cytotoxic effect against HepG-2, SK-LU-1 and MCF-7 with IC50 values of 8.20, 6.66 and 9.35 µM, respectively. Results: The bioassay result showed that several compounds exhibited cytotoxic effects against three human cancer cell lines including HepG-2, SK-LU-1 and MCF-7. Especially, compound 9a displayed the best cytotoxic effect against HepG-2, SK-LU-1 and MCF-7 with IC50 values of 8.20, 6.66 and 9.35 µM, respectively. Conclusion: The research results suggest that some compounds could be considered as a lead for future design of zerumbone hydrazones in which bio-isosteric replacements in ortho position of the phenyl ring could be performed to improve the cytotoxic activity.

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Design, Synthesis and In vitro Cytotoxic Evaluation of Novel Hybrids of Artemisinin and Quinazolinone

Letters in Organic Chemistry ◽

10.2174/1570178618666211001115131 ◽

2021 ◽

Vol 18 ◽

Author(s):

Tran Khac Vu ◽

Bach Xuan Nguyen ◽

Linh Nguyen Pham Duy ◽

Thuc Bao Nguyen Truong ◽

Anh Tuan Phung ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Anti Cancer ◽

Ic50 Values ◽

Mcf 7

Background: In this study, two novel hybrid series of artemisinin and quinazolinones were synthesized and evaluated in vitro cytotoxicity against two human cancer cell lines, including SKLu-1 (lung cancer), MCF- 7 (breast cancer). The bio-assay results indicated that most of the target compounds exhibited cytotoxic activities against both human cancer cell lines tested, and seemed to be more cytotoxic toward the breast (MCF-7) cancer cells than lung (SKLu-1) cancer cells. Among the synthesized artemisinin hybrids, the compound 13d containing a quinazolinone conjugated system exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 µM, respectively. Objective: This study aims at developing novel hybrids of artemisinin and quinazolinones as anti-cancer agents. Method: A series of novel hybrids were designed, synthesized and evaluated for cytotoxicity against two human cancer cell lines, including SKLu-1 and MCF-7 using SRB method. Results : All thirteen hybrids of artemisinin with quinazolinone exhibited cytotoxic activity against two tested cancer cell lines, in which the compound 13d exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 µM, respectively. Conclusion: The research results suggest that some compounds could be considered as leads for future design of hybrids and have the potential for further studies in the field of anti-cancer agent development.

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

Medicinal Chemistry ◽

10.2174/1573406414666180828124252 ◽

2019 ◽

Vol 15 (4) ◽

pp. 352-359 ◽

Cited By ~ 3

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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CYTOTOXICITY OF FIVE PLANT EXTRACTS AGAINST DIFFERENT HUMAN CANCER CELL LINES AND THEIR MOLECULAR MECHANISM

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2020.v13i10.38698 ◽

2020 ◽

pp. 194-198

Author(s):

SALWA EL-HALLOUTY ◽

ASHWAQ BATAWI ◽

MANAL SHAFI ◽

ESAM RASHWAN ◽

EZZELDIN ELHAWARY ◽

...

Keyword(s):

Cell Lines ◽

Plant Extracts ◽

Normal Cell ◽

Human Cancer ◽

Human Tumor ◽

Human Cancer Cell Lines ◽

Hct 116 ◽

Bax Gene ◽

Mcf 7

Objective: Five methanol plant extracts namely, Euphorbia hierosolymitana, Dracaena marginata, Cordyline terminalis, and Sapium sebifera were screened in vitro for their cytotoxic effect on human tumor cell lines; namely, PC-3, HepG-2, HCT-116, and MCF-7 (prostate, liver, colon, and breast cancer) and human normal cell lines, namely, BJ-1. Methods: E. hierosolymitana (extract A) selectively inhibited HCT-116 cell proliferation with IC50 of 4.22 μg/ml, both Dracaena marginata (extract B) (bark, leaves, and branches) showed moderate cytotoxicity on MCF-7 with IC50 of 22.4 and 48.2 μg/ml, respectively. The remaining two extracts showed minimal to insignificant percentage inhibition on all cell lines. Results: E. hierosolymitana extract was selected for further studying, where the effect of the extract on the HCT116 cells showed a downregulation of her2 and Bcl-2 gene and overexpression of the Bax gene. Flow cytometry analysis was also performed to understand the effect of E. hierosolymitana on the apoptosis induction and the cell cycle. The results showed the induction of early and late apoptosis by 5.81 and 10.01%, respectively. Conclusion: Our results infer that E. hierosolymitana has a promising chance in fighting colorectal cancer due to its high cytotoxic effects on HCT116 cancer cells while having minimal effects on the BJ-1 normal cell lines.

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Anticancer Evaluation of Tris(triazolyl)triazine Derivatives Generated via Click Chemistry

Australian Journal of Chemistry ◽

10.1071/ch16006 ◽

2016 ◽

Vol 69 (8) ◽

pp. 905 ◽

Cited By ~ 8

Author(s):

Tamer El Malah ◽

Hany F. Nour ◽

A. A. Nayl ◽

R. A. Elkhashab ◽

Farouk M. E. Abdel-Megeid ◽

...

Keyword(s):

Click Chemistry ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Standard Drug ◽

Human Cancer Cell Lines ◽

Triazine Derivatives ◽

Mcf 7

Click chemistry has been utilised for the preparation of new tris(triazolyl)triazines containing aliphatic and polar side chains through coupling of 2,4,6-triethynyl-[1,3,5]triazines, which possess free terminal alkyne moieties with substituted aromatic azides. The cytotoxic activity and in vitro anticancer potential of the newly synthesised compounds have been evaluated against seven human cancer cell lines including liver HepG2, breast MCF-7, lung A549, acute myeloid leukemia HL-60, colon HCT116, and prostate PC3 cancer cell lines in addition to human normal melanocyte, HFB4. The results revealed that all the compounds did not exhibit any activity against A549, HL-60, and PC3. However compound G2 was effective against MCF-7 and HepG2 cancer cell lines. On the other hand, compound G1a exhibited higher potency against MCF-7 and HepG2 cells with no toxicity on normal cells in comparison with the standard drug doxorubicin.

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