scholarly journals In-Vitro and In-Silico Evaluations of Heterocyclic-Containing Diarylpentanoids as Bcl-2 Inhibitors Against LoVo Colorectal Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3877
Author(s):  
Sze Wei Leong ◽  
Suet Lin Chia ◽  
Faridah Abas ◽  
Khatijah Yusoff
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
M Cell ◽  
Apoptosis Assay ◽  
Ic50 Values

In the present study, we investigated the in-vitro anti-cancer potential of six diarylpentanoids against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, SW620, LoVo, HT29, NCI-H508, RKO, and LS411N cells. Structure–activity relationship study suggested that the insertions of tetrahydro-4H-thiopyran-4-one and brominated phenyl moieties are essential for better cytotoxicity. Among the evaluated analogs, 2e has been identified as the lead compound due to its low IC50 values of approximately 1 µM across all cancer cell lines and high chemotherapeutic index of 7.1. Anti-proliferative studies on LoVo cells showed that 2e could inhibit cell proliferation and colony formations by inducing G2/M cell cycle arrest. Subsequent cell apoptosis assay confirmed that 2e is a Bcl-2 inhibitor that could induce intrinsic cell apoptosis by creating a cellular redox imbalance through its direct inhibition on the Bcl-2 protein. Further molecular docking studies revealed that the bromophenyl moieties of 2e could interact with the Bcl-2 surface pocket through hydrophobic interaction, while the tetrahydro-4H-thiopyran-4-one fragment could form additional Pi-sulfur and Pi-alkyl interactions in the same binding site. In all, the present results suggest that 2e could be a potent lead that deserves further modification and investigation in the development of a new Bcl-2 inhibitor.

Precision cancer therapy through nanoparticle delivery of siRNA against KRAS.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 260-260
Author(s):  
Matthew S. Strand ◽  
Hua Pan ◽  
Julie G. Grossman ◽  
Peter S. Goedegebuure ◽  
Timothy Fleming ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colorectal Cancers ◽  
Mouse Pancreas ◽  
Colorectal Cancer Cell Lines ◽  
Human And Mouse

260 Background: Small interfering RNA (siRNA) has potential for highly specific gene manipulation, making it attractive for delivering precision therapy to cancer patients. However, efforts to employ siRNA therapeutically have been limited by its short half-life in circulation, low target tissue specificity, and cellular entrapment within endosomes. We utilized serum-stable, cell-penetrating, and endosomolytic peptide-based nanoparticles (NPs) to overcome these obstacles and deliver siRNA against KRAS to KRAS-mutant human and mouse pancreas and colorectal cancers. Methods: Human and mouse pancreas and colorectal cancer cell lines were tested for NP uptake in vitro utilizing fluorescent siRNAs. Uptake was assessed via fluorescent microscopy and flow cytometry (FC). Mice bearing tumors from these cells were injected IV with the same NP, and uptake was assessed with an in vivo imaging system (IVIS), and FC. Cell lines were treated with KRAS-siRNA NP and KRAS knockdown was assessed by real-time PCR. Results: Mouse and human pancreas and colorectal cancer cell lines took up NP in vitro, with signal detected within > 93% of cells at 24 hours. Tumors from these cells grown in mice were strongly fluorescent after IV injection of fluorescent NP within 2 hours, and until at least 30 hours. FC of a tumor treated with fluorescent NP showed that 86% of tumor cells expressed fluorescent signal 24 hours post-injection. IVIS revealed signal in mouse liver and kidneys, but when assessed by FC, only 17.8% and 13.5% of cells from these tissues were fluorescent, respectively. The brain, heart, lungs, spleen, and pancreas of mice receiving injections were negative. Cancer cell lines exposed to KRAS-siRNA NP for 48 hours express KRAS at levels that are 4.5 to 15.1% of untreated cells. Conclusions: Human and mouse pancreas and colorectal cancers efficiently and specifically take up NP in vitro and in vivo. Selected limitations of siRNA are overcome with this NP delivery system, and NP-packaged siRNA effectively inhibits KRAS. This platform represents a highly specific approach to targeting tumor genes of interest, which may ultimately enable selective knockdown of putative drivers of tumor progression.

scholarly journals Design, Synthesis, and In Vitro Antiproliferative Activity of Hydantoin and Purine Derivatives with the 4-Acetylphenylpiperazinylalkyl Moiety

Materials ◽  
2021 ◽  
Vol 14 (15) ◽  
pp. 4156
Author(s):  
Agnieszka Zagórska ◽  
Anna Czopek ◽  
Anna Jaromin ◽  
Magdalena Mielczarek-Puta ◽  
Marta Struga ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
Chemical Diversity ◽  
Cancer Drug ◽  
Purine Derivatives ◽  
Design Synthesis ◽  
Cancer Drug Discovery

Cancer represents one of the most serious health problems and the second leading cause of death around the world. Heterocycles, due to their prevalence in nature as well as their structural and chemical diversity, play an immensely important role in anti-cancer drug discovery. In this paper, a series of hydantoin and purine derivatives containing a 4-acetylphenylpiperazinylalkyl moiety were designed, synthesized, and biologically evaluated for their anticancer activity on selected cancer cell lines (PC3, SW480, SW620). Compound 4, a derivative of 3′,4′-dihydro-2′H-spiro[imidazolidine-4,1′-naphthalene]-2,5-dione, was the most effective against SW480, SW620, and PC3 cancer cell lines. Moreover, 4 has high tumor-targeting selectivity. Based on docking studies, it was concluded that R isomers of 3′,4′-dihydro-2′H-spiro[imidazolidine-4,1′-naphthalene]-2,5-dione could be further studied as promising scaffolds for the development of thymidine phosphorylase inhibitors.

scholarly journals NEW QUINAZOLINONE DERIVATIVES: SYTHESIS AND IN VITRO CYTOTOXIC ACTIVITY

2020 ◽  
Vol 58 (1) ◽  
pp. 12
Author(s):  
Tran Khac Vu
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cytotoxic Effect ◽  
Cancer Cell Lines ◽  
Ic50 Values ◽  
Quinazolinone Derivatives ◽  
Bioassay Result ◽  
Mcf 7

The paper presents a simple synthesis of new quinazolinone derivatives 13a-i. Synthesized derivatives were tested for their cytotoxic effect against three cancer cell lines including SKLU-1, MCF-7 and HepG-2. The bioassay result showed that only compound 13e exhibited significant cytotoxic effect against cancer cell lines tested with IC50 values of 9.48, 20.39 and 18.04 µg/ mL, respectively.

Morindone From Morinda Citrifolia as a Potential Antiproliferative Agent Against Colorectal Cancer Cell Lines

2021 ◽  
Author(s):  
Cheok Wui Chee ◽  
Nor hisam Zamakshshari ◽  
Vannajan Lee ◽  
Iskandar Abdullah ◽  
Rozana Othman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
In Silico ◽  
Cancer Cell Lines ◽  
Morinda Citrifolia ◽  
Colorectal Cancer Cell ◽  
Root Bark ◽  
Colorectal Cancer Cell Lines

Abstract There is an increasing demand in developing new, effective, and affordable anti-cancer against colon and rectal. In this study, our aim is to identify the potential anthraquinone compounds from the root bark of Morinda citrifolia to be tested in vitro against colorectal cancer cell lines. Eight potential anthraquinone compounds were successfully isolated, purified and tested for both in-silico and in-vitro analyses. Based on the in-silico prediction, two anthraquinones, morindone and rubiadin, exhibit a comparable binding affinity towards multitargets of β-catenin, MDM2-p53 and KRAS. Subsequently, we constructed a 2D interaction analysis based on the above results and it suggests that the predicted anthraquinones from Morinda citrifolia offer an attractive starting point for potential antiproliferative agents against colorectal cancer. In vitro analyses further indicated that morindone and damnacanthal have significant cytotoxicity effect and selectivity activity against colorectal cancer cell lines.

Synthesis and anticancer activity of thiadiazole containing thiourea, benzothiazole and imidazo[2,1-b][1,3,4]thiadiazole scaffolds

2020 ◽  
Vol 16 ◽  
Author(s):  
Stephen Paul Avvaru ◽  
Malleshappa N. Noolvi ◽  
Uttam A More ◽  
Sudipta Chakraborty ◽  
Ashutosh Dash ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agents ◽  
Data Bank ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
Human Leukemia

Background: A great array of nitrogen-containing heterocyclic rings were being extensively explored for their functional versatility in the field of medicine especially in anticancer research. 1,3,4-thiadiazole is one of such heterocyclic ring with promising anticancer activity against several cancer cell lines, inhibiting diverse biological targets. Introduction: The 1,3,4-thiadiazole, when equipped with other heterocyclic scaffolds, has displayed enhanced anticancer properties. The thiourea, benzothiazole, imidazo[2,1,b][1,3,4]-thiadiazoles are such potential scaffolds with promising anticancer activity. Method: A new series of 5-substituted-1,3,4-thiadiazoles linked with phenyl thiourea, benzothiazole and 2,6-disubstituted imidazo[2,1- b][1,3,4]thiadiazole derivatives were synthesized and tested for in-vitro anticancer activity on various cancer cell lines. Results: The National Cancer Institute’s preliminary anticancer screening results showed compounds 4b and 5b having potent antileukemic activity. Compound 4b selectively showed 32 percent lethality on Human Leukemia-60 cell line. The docking studies of the derivatives on aromatase enzyme (Protein Data Bank: 3S7S) have shown reversible interactions at the active site with good docking scores comparable to Letrozole and Exemestane. Further, the selected derivatives were tested for anticancer activity on HeLa cell line based on the molecular docking studies. Conclusion: Compound 4b and 5b showed effective inhibition equivalent to Letrozole. These preliminary biological screening studies have given positive anticancer activity for these new classes of derivatives. An additional research study like the mechanism of action of the anticancer activity of this new class of compounds is necessary. These groundwork studies illuminate a future pathway for research of this class of compounds enabling the discovery of potent antitumor agents.

Sign in / Sign up

Export Citation Format

Share Document