Structure–Activity Studies on the Spiroketal Moiety of a Simplified Analogue of Debromoaplysiatoxin with Antiproliferative Activity

2012 ◽  
Vol 55 (11) ◽  
pp. 5614-5626 ◽  
Author(s):  
Masayuki Kikumori ◽  
Ryo C. Yanagita ◽  
Harukuni Tokuda ◽  
Nobutaka Suzuki ◽  
Hiroshi Nagai ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Structure Activity

scholarly journals Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1380
Author(s):  
Xiutao Wu ◽  
Lijie Gong ◽  
Chen Chen ◽  
Ye Tao ◽  
Wuxi Zhou ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Normal Cell ◽  
Selectivity Index ◽  
Cytotoxic Activities ◽  
Structure Activity ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Hct 116 ◽  
Systematic Structure

Harringtonolide (HO), a natural product isolated from Cephalotaxus harringtonia, exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure−activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone, and allyl positions of HO (1) were carried out to provide 17 derivatives (2–13, 11a–11f). The in vitro antiproliferative activity against four cancer cell lines (HCT-116, A375, A549, and Huh-7) and one normal cell line (L-02) was tested. Amongst these novel derivatives, compound 6 exhibited comparable cell growth inhibitory activity to HO and displayed better selectivity index (SI = 56.5) between Huh-7 and L-02 cells. The SAR results revealed that the tropone and lactone moieties are essential for the cytotoxic activities, which provided useful suggestions for further structural optimization of HO.

scholarly journals Development of CDK4/6 Inhibitors: A Five Years Update

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1488
Author(s):  
Alessandra Ammazzalorso ◽  
Mariangela Agamennone ◽  
Barbara De Filippis ◽  
Marialuigia Fantacuzzi
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Effects ◽  
Antiproliferative Activity ◽  
Treatment Efficacy ◽  
Metastatic Breast ◽  
Breast Cancer Treatment ◽  
Survival Outcomes ◽  
Cyclin Dependent Kinases ◽  
Structure Activity

The inhibition of cyclin dependent kinases 4 and 6 plays a role in aromatase inhibitor resistant metastatic breast cancer. Three dual CDK4/6 inhibitors have been approved for the breast cancer treatment that, in combination with the endocrine therapy, dramatically improved the survival outcomes both in first and later line settings. The developments of the last five years in the search for new selective CDK4/6 inhibitors with increased selectivity, treatment efficacy, and reduced adverse effects are reviewed, considering the small-molecule inhibitors and proteolysis-targeting chimeras (PROTACs) approaches, mainly pointing at structure-activity relationships, selectivity against different kinases and antiproliferative activity.

Antiproliferative activity of cardenolides on cell line A549: structure–activity relationship analysis

2020 ◽  
Author(s):  
Salvador Enrique Meneses-Sagrero ◽  
Luisa Alondra Rascón-Valenzuela ◽  
Rogerio Sotelo-Mundo ◽  
Wagner Vilegas ◽  
Carlos Velazquez ◽  
...  
Keyword(s):  
Cell Line ◽  
Antiproliferative Activity ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Relationship Analysis ◽  
Structure Activity

Imidazopyridine-fused [1,3]-diazepinones part 2: Structure-activity relationships and antiproliferative activity against melanoma cells

2017 ◽  
Vol 125 ◽  
pp. 1225-1234 ◽  
Author(s):  
Virginie Bellet ◽  
Laure Lichon ◽  
Dominique P. Arama ◽  
Audrey Gallud ◽  
Vincent Lisowski ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Melanoma Cells ◽  
Structure Activity Relationships ◽  
Structure Activity

Antiproliferative activity in HL60 cells by tetrasubstituted pyrroles: a structure–activity relationship study

2005 ◽  
Vol 15 (10) ◽  
pp. 2487-2490 ◽  
Author(s):  
José M. Padrón ◽  
David Tejedor ◽  
Alicia Santos-Expósito ◽  
Fernando García-Tellado ◽  
Víctor S. Martín ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Hl60 Cells ◽  
Structure Activity ◽  
Relationship Study

scholarly journals Anticancer and Structure Activity Relationship of Non-Symmetrical Choline Kinase Inhibitors

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1360
Author(s):  
Santiago Schiaffino-Ortega ◽  
Elena Mariotto ◽  
Pilar María Luque-Navarro ◽  
María Kimatrai-Salvador ◽  
Pablo Rios-Marco ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Kinase Inhibitors ◽  
Human Tumor ◽  
Structure Activity Relationship ◽  
Inhibitory Effect ◽  
Activity Relationship ◽  
Choline Kinase ◽  
Choline Uptake ◽  
Uptake Inhibition ◽  
Structure Activity

Choline kinase inhibitors are an outstanding class of cytotoxic compounds useful for the treatment of different forms of cancer since aberrant choline metabolism is a feature of neoplastic cells. Here, we present the most in-depth structure-activity relationship studies of an interesting series of non-symmetric choline kinase inhibitors previously reported by our group: 3a–h and 4a–h. They are characterized by cationic heads of 3-aminophenol bound to 4-(dimethylamino)- or 4-(pyrrolidin-1-yl)pyridinium through several linkers. These derivatives were evaluated both for their inhibitory activity on the enzyme and their antiproliferative activity in a panel of six human tumor cell lines. The compounds with the N-atom connected to the linker (4a–h) show the best inhibitory results, in the manner of results supported by docking studies. On the contrary, the best antiproliferative compounds were those with the O-atom bounded to the linker (3a–h). On the other hand, as was predictable in both families, the inhibitory effect on the enzyme is better the shorter the length of the linker. However, in tumor cells, lipophilicity and choline uptake inhibition could play a decisive role. Interestingly, compounds 3c and 4f, selected for both their ability to inhibit the enzyme and good antiproliferative activity, are endowed with low toxicity in non-tumoral cells (e.g., human peripheral lymphocytes) concerning cancer cells. These compounds were also able to induce apoptosis in Jurkat leukemic cells without causing significant variations of the cell cycle. It is worth mentioning that these derivatives, besides their inhibitory effect on choline kinase, displayed a modest ability to inhibit choline uptake thus suggesting that this mechanism may also contribute to the observed cytotoxicity.

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