Hydroxamic acid derivatives as HDAC1, HDAC6 and HDAC8 inhibitors with antiproliferative activity in cancer cell lines

A series of eight polymethoxychalcone Mannich base derivatives 2a-2h was synthesized via the microwave-assisted Mannich reaction of natural product 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1) with various secondary amines and formaldehyde. Compared to conventional heating method (80°C), the microwave-assisted method (700W, 65°C) is efficient with short reaction time (0.5-1 h) and good yields (74-88%). The antiproliferative activities of eight Mannich base derivatives were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3) by CCK-8 assay. The results showed that all of the Mannich base derivatives exhibited potential antiproliferative activities on tested cancer cell lines with the IC50 values of 9.13-48.51 µM. Some active compounds exhibited more activity as compared to positive control cis-Platin. Among them, compound 2b revealed to have the strongest antiproliferative activity against all the three cancer cell lines with IC50 values ranging from 9.13 to 11.24 µM.

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Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽

10.3390/molecules26071838 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1838

Author(s):

Naglaa M. Ahmed ◽

Mahmoud M. Youns ◽

Moustafa K. Soltan ◽

Ahmed M. Said

Keyword(s):

Molecular Modeling ◽

Antitumor Activity ◽

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Antitumor Agents ◽

Cancer Cell Lines ◽

Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

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An IMDAF approach to annellated 1,4:5,8-diepoxynaphthalenes and their metathesis reaction leading to novel scaffolds displaying an antiproliferative activity toward cancer cells

New Journal of Chemistry ◽

10.1039/d1nj03991a ◽

2021 ◽

Author(s):

Elizaveta A. Kvyatkovskaya ◽

Kseniya K. Borisova ◽

Polina P. Epifanova ◽

Aleksey A. Senin ◽

Victor N. Khrustalev ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Metathesis Reaction ◽

Human Cancer Cell Lines ◽

Antiproliferative Agent

A 3,5a-epoxyfuro[2,3,4-de]isoquinoline scaffold, the product of ROCM of 1,4:5,8-diepoxynaphthalenes, is a promising antiproliferative agent toward breast and prostate human cancer cell lines.

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Antiproliferative activity of the Netherlands propolis and its active principles in cancer cell lines

Journal of Ethnopharmacology ◽

10.1016/s0378-8741(02)00022-3 ◽

2002 ◽

Vol 80 (1) ◽

pp. 67-73 ◽

Cited By ~ 94

Author(s):

Arjun H Banskota ◽

Takema Nagaoka ◽

Lucia Yoshie Sumioka ◽

Yasuhiro Tezuka ◽

Suresh Awale ◽

...

Keyword(s):

The Netherlands ◽

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Cancer Cell Lines

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Click Synthesis, Anticancer Activity, and Molecular Docking Investigation of some Functional 1,2,3-triazole Derivatives

Biointerface Research in Applied Chemistry ◽

10.33263/briac126.76337667 ◽

2021 ◽

Vol 12 (6) ◽

pp. 7633-7667

Keyword(s):

Cell Cycle ◽

Molecular Docking ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Antiproliferative Activity ◽

Cancer Cell Lines ◽

Reference Drug ◽

Active Inhibitor ◽

Triazole Derivatives

1,2,3-triazole skeleton is a privileged building block for the discovery of new promising anticancer agents. In this report, new 1,4-disubstituted 1,2,3-triazoles with the bioisoster triazole moiety were straightforwardly prepared under copper-catalyzed azide-alkyne [3+2] cycloaddition reactions (CuAAC) regime using a variety of both functional organic azides and terminal alkynes. The resulting functional 1,4-disubstituted 1,2,3-triazole compounds were fully characterized and subsequently tested for their antiproliferative activity against four different cancer cell lines. The cytotoxicity tests carried out with these 1,2,3-triazole derivatives show average IC50 values ranging from 15 to 50 µM by comparison with the standard reference drug, namely doxorubicin. The phosphonate 1,2,3-triazole derivative was found to exhibit the best antiproliferative activity among the studied compounds against the HT-1080 cell lines. It was chosen to evaluate its mode of action in these cancer cell lines. The cell cycle study showed that the phosphonate derivative, compound 8, is the most active inhibitor of the cell cycle at the G0/G1 phase, inducing apoptosis independently of Caspase-3 and causing an increase in the mitochondrial membrane potential (ΔΨm) in the HT-1080 cell lines. Molecular docking studies of this phosphonate derivative into the MMP-2 and MMP-9 metalloproteinases receptors demonstrated the relevance of triazole scaffolds and the pendant phosphonate group in establishing -anion, -alkyl and hydrogen bonding type interactions with residual components in the active MMP pocket.

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Synthesis of Lapachol-Based Glycosides and Glycosyl Triazoles with Antiproliferative Activity Against Several Cancer Cell Lines

10.21203/rs.3.rs-916974/v1 ◽

2021 ◽

Author(s):

Flaviano Melo Ottoni ◽

Lucas Bonfim Marques ◽

Juliana Martins Ribeiro ◽

Lucas Lopardi Franco ◽

José Dias Souza Filho ◽

...

Keyword(s):

Antitumor Activity ◽

Adverse Effects ◽

Dna Fragmentation ◽

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Biological Activities ◽

Cancer Cell Lines ◽

Tumor Cell Lines

Abstract Lapachol (1), a natural naphthoquinone, presents several biological activities including antitumor activity, used as anticancer coadjuvant whose use was abandoned because of adverse effects. Herein, we reported the synthesis and cytotoxicity evaluation against cancer cell lines of a series of Oglycosides and glycosyl triazoles derived from lapachol. In addition to the determination of IC50, the DNA fragmentation and clonogenicity were also evaluated. The glycoside derived from D-glucose (5) was far more active than lapachol (1) and more active in tumor cell lines HL60, Jurkat, THP-1 and MDA-MB-231 than to the non-tumoral PBMC cell line, indicating an improvement in activity and selectivity as compared with lapachol (1). Compound 5 and the glycosides derived from D-galactose (14), D-N-acetylglucosamine (15) and L-fucose (16) showed good results in the DNA fragmentation and clonogenicity assays in the studies of subdiploid DNA content, indicating a pro-apoptotic potential and a good antiproliferative activity of these glycosides.

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Novel N-(2-Mercaptobenzenesulfonyl)guanidine Derivatives Modified by Nitrogen-containing Heterocycles – Synthesis and Antiproliferative Activity Against Human Cancer Cell Lines

10.3390/ecmc-3-04675 ◽

2017 ◽

Author(s):

Aneta Pogorzelska ◽

Jarosław Sławiński ◽

Anna Kawiak ◽

Joanna Jasińska

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Guanidine Derivatives

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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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