Synthesis and In Vitro Antiproliferative Activity of Diphenyl(piperidin-4- yl)thioamide Methanol Derivatives

Novel imidazole derivatives were designed, prepared, and evaluated in vitro for antitumor activity. The majority of the tested derivatives showed improved antiproliferative activity compared to the positive control drugs 5-FU and MTX. Among them, compound 4f exhibited outstanding antiproliferative activity against three cancer cell lines and was considerably more potent than both 5-FU and MTX. In particular, the selectivity index indicated that the tolerance of normal L-02 cells to 4f was 23–46-fold higher than that of tumor cells. This selectivity was significantly higher than that exhibited by the positive control drugs. Furthermore, compound 4f induced cell apoptosis by increasing the protein expression levels of Bax and decreasing those of Bcl-2 in a time-dependent manner. Therefore, 4f could be a potential candidate for the development of a novel antitumor agent.

Download Full-text

Design, Synthesis, and In Vitro Evaluation of Tubulin‐targeting Dibenzothiazines with Antiproliferative Activity as Novel Heterocycle Building Block

ChemMedChem ◽

10.1002/cmdc.202100383 ◽

2021 ◽

Author(s):

Walter Damián Guerra ◽

Daniel Lucena-Agell ◽

Rafael Hortigüela ◽

Roberto Arturo Rossi ◽

J. Fernando Díaz ◽

...

Keyword(s):

Antiproliferative Activity ◽

Building Block ◽

Design Synthesis ◽

In Vitro Evaluation

Download Full-text

Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity

Molecules ◽

10.3390/molecules26051380 ◽

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.

Download Full-text

Antitumor Potential of Lippia citriodora Essential Oil in Breast Tumor-Bearing Mice

Antioxidants ◽

10.3390/antiox10060875 ◽

2021 ◽

Vol 10 (6) ◽

pp. 875

Author(s):

Katerina Spyridopoulou ◽

Tamara Aravidou ◽

Evangeli Lampri ◽

Eleni Effraimidou ◽

Aglaia Pappa ◽

...

Keyword(s):

Breast Cancer ◽

Antiproliferative Activity ◽

Folk Medicine ◽

Tumor Model ◽

Flowering Plant ◽

Antitumor Effects ◽

Lippia Citriodora ◽

Antitumor Potential ◽

Apoptotic Marker

Lippia citriodora is a flowering plant cultivated for its lemon-scented leaves and used in folk medicine for the preparation of tea for the alleviation of symptoms of gastrointestinal disorders, cold, and asthma. The oil extracted from the plant leaves was shown to possess antioxidant potential and to exert antiproliferative activity against breast cancer. The aim of this study was to further investigate potential antitumor effects of L. citriodora oil (LCO) on breast cancer. The in vitro antiproliferative activity of LCO was examined against murine DA3 breast cancer cells by the sulforhodamine B assay. We further explored the LCO’s pro-apoptotic potential with the Annexin-PI method. The LCO’s anti-migratory effect was assessed by the wound-healing assay. LCO was found to inhibit the growth of DA3 cells in vitro, attenuate their migration, and induce apoptosis. Finally, oral administration of LCO for 14 days in mice inhibited by 55% the size of developing tumors in the DA3 murine tumor model. Noteworthy, in the tumor tissue of LCO-treated mice the apoptotic marker cleaved caspase-3 was elevated, while a reduced protein expression of survivin was observed. These results indicate that LCO, as a source of bioactive compounds, has a very interesting nutraceutical potential.

Download Full-text

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.

Download Full-text

Potential Anticancer Lipoxygenase Inhibitors from the Red Sea-Derived Brown Algae Sargassum cinereum: An In-Silico-Supported In-Vitro Study

Antibiotics ◽

10.3390/antibiotics10040416 ◽

2021 ◽

Vol 10 (4) ◽

pp. 416

Author(s):

Sami I. Alzarea ◽

Abeer H. Elmaidomy ◽

Hani Saber ◽

Arafa Musa ◽

Mohammad M. Al-Sanea ◽

...

Keyword(s):

Red Sea ◽

Antiproliferative Activity ◽

Inhibitory Activity ◽

Brown Algae ◽

In Silico ◽

Active Sites ◽

In Vitro Study ◽

Lipoxygenase Inhibitors ◽

Phytochemical Investigation

LC-MS-assisted metabolomic profiling of the Red Sea-derived brown algae Sargassum cinereum “Sargassaceae” dereplicated eleven compounds 1–11. Further phytochemical investigation afforded two new aryl cresol 12–13, along with eight known compounds 14–21. Both new metabolites, along with 19, showed moderate in vitro antiproliferative activity against HepG2, MCF-7, and Caco-2. Pharmacophore-based virtual screening suggested both 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The in vitro enzyme assays revealed 12 and 13 were able to inhibit 5-LOX more preferentially than 15-LOX, while 19 showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico investigation revealed the molecular interactions inside both enzymes’ active sites and explained the varying inhibitory activity for 12 and 13 toward 5-LOX and 15-LOX.

Download Full-text

Wild pink bayberry fruit: the effect of in vitro gastrointestinal digestion on phytochemical profiles, and antioxidant and antiproliferative activities

Food & Function ◽

10.1039/d0fo02370a ◽

2021 ◽

Author(s):

Wen Xia ◽

Yanyun Lin ◽

Ersheng Gong ◽

Tong Li ◽

Fengli Lian ◽

...

Keyword(s):

Dietary Supplement ◽

Antiproliferative Activity ◽

Gastrointestinal Digestion ◽

In Vitro Gastrointestinal Digestion ◽

Phytochemical Profiles ◽

Antiproliferative Activities

In general, pink bayberry cultivar, a vital source of polyphenols, showed strong antiproliferative activity after digestion at the end of the intestinal and colon steps, which can be considered as a dietary supplement.

Download Full-text

Antiproliferative Activity and Potential Mechanism of Marine-Sourced Streptoglutarimide H against Lung Cancer Cells

Marine Drugs ◽

10.3390/md19020079 ◽

2021 ◽

Vol 19 (2) ◽

pp. 79

Author(s):

Hengju Ge ◽

Di Zhang ◽

Muran Shi ◽

Xiaoyuan Lian ◽

Zhizhen Zhang

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Antiproliferative Activity ◽

Lung Cancer Cells ◽

Potential Mechanism ◽

Nucleotide Synthesis ◽

Factor C ◽

Antiglioma Activity

In 2019, streptoglutarimide H (SGH) was characterized as a new glutarimide from the secondary metabolites produced by a marine-derived actinomycete Streptomyces sp. ZZ741 and shown to have in vitro antiglioma activity. However, the antiproliferative activity and potential mechanism of SGH against lung cancer cells have not yet been characterized. This study demonstrated that SGH significantly inhibited the proliferation of different lung cancer cells. In terms of mechanism of action, SGH downregulated cell cycle- and nucleotide synthesis-related proteins to block cell cycle at G0/G1 phase, reduced the expression levels of glycolytic metabolic enzymes to inhibit glycolysis, and downregulated the important cancer transcription factor c-Myc and the therapeutic target deubiquitinase USP28. Potent anticancer activity and multiple mechanisms indicated SGH to be a novel antitumor compound against lung cancer cells.

Download Full-text