scholarly journals A Profile of the In Vitro Anti-Tumor Activity and In Silico ADME Predictions of Novel Benzothiazole Amide-Functionalized Imidazolium Ionic Liquids

2019 ◽  
Vol 20 (12) ◽  
pp. 2865 ◽  
Author(s):  
Fawzia Al-blewi ◽  
Nadjet Rezki ◽  
Arshi Naqvi ◽  
Husna Qutb Uddin ◽  
Salsabeel Al-Sodies ◽  
...  
Keyword(s):  
Ionic Liquids ◽  
In Silico ◽  
Human Cancer ◽  
Biological Data ◽  
Anticancer Activities ◽  
Imidazolium Ionic Liquids ◽  
Human Cancer Cell Lines ◽  
Colon Cancers ◽  
Cancer Types

A focused array of green imidazolium ionic liquids (ILs) encompassing benzothiazole ring and amide linkage were designed and synthesized using quaternization and metathesis protocols. The synthesized ILs have been fully characterized by usual spectroscopic methods and screened for their anticancer activities against human cancer cell lines originating from breast and colon cancers. Collectively, our biological data demonstrate that the newly synthesized series has variable anticancer activities in the examined cancer types. The synthesized ILs 8, 10 and 21–29 comprising the methyl and methyl sulfonyl benzothiazole ring emerged as the most potent compounds with promising antiproliferative activities relative to their benzothiazole ring counterparts. Furthermore, the mechanism underlying the observed anticancer activity was investigated. The most active compound 22 appears to exert its anticancer effect through apoptosis dependent pathway in breast cancer cells. Interestingly, compound 22 has also shown good in silico absorption (81.75%) along with high gastro-intestinal absorption as per ADME predictions.

scholarly journals Novel Fluorinated Imidazolium Ionic Liquids: Eco-friendly, Facile and Efficient Construction, Characterization, in vitro Anticancer Activity, Toxicity and in silico Analysis

2020 ◽  
Vol 32 (3) ◽  
pp. 690-696 ◽  
Author(s):  
Ahmed H. Albalawi ◽  
Saud M. Almutairi ◽  
Ateyatallah Aljuhani ◽  
Pramod K. Sahu ◽  
Praveen K. Sahu ◽  
...  
Keyword(s):  
Ionic Liquids ◽  
In Silico ◽  
Human Cancer ◽  
Chemical Properties ◽  
In Silico Analysis ◽  
Human Cancer Cell Lines ◽  
Ic50 Values ◽  
Efficient Construction ◽  
Silico Analysis

An efficient and facile synthesis of novel fluorinated imidazolium-tagged ionic liquids under microwave irradiation is described. Novel prepared ionic liquids was identified and confirmed by spectroscopic and elemental analysis. Synthesized ionic liquids (1-12) was explored for their antiproliferative inhibition potency against three selected human cancer cell lines (MCF-7, HepG-2 and CACO2). Screening results have revealed that some tested ionic liquids exhibited promising activity compared with standard drugs, especially compounds 5 and 6 which consistently produced low IC50 values. Preliminary structure activity relationship (SAR) studies have been performed to identify the relation between molecular structure and activity. in silico Analysis of ionic liquids was carried out based on ADME, Lipinski rule, drug likeness, toxicity profiles and other physico-chemical properties. All compounds were safe in toxicity profile and computed LD50 values were in accepted range (2.55-2.89 mol/kg). in silico Results have shown that Lipinski rule of five was in accept range, except compound 1 and 2.

scholarly journals Synthesis, Characterization, and Preliminary In Vitro Cytotoxic Evaluation of a Series of 2-Substituted Benzo [d] [1,3] Azoles

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2780
Author(s):  
Ozvaldo Linares-Anaya ◽  
Alcives Avila-Sorrosa ◽  
Francisco Díaz-Cedillo ◽  
Luis Ángel Gil-Ruiz ◽  
José Correa-Basurto ◽  
...  
Keyword(s):  
Binding Site ◽  
In Silico ◽  
Cytotoxic Effect ◽  
Human Cancer ◽  
Cytotoxic Activities ◽  
Human Cancer Cell ◽  
Inhibitory Effects ◽  
Reference Drug ◽  
Human Cancer Cell Lines

A series of benzo [d] [1,3] azoles 2-substituted with benzyl- and allyl-sulfanyl groups were synthesized, and their cytotoxic activities were in vitro evaluated against a panel of six human cancer cell lines. The results showed that compounds BTA-1 and BMZ-2 have the best inhibitory effects, compound BMZ-2 being comparable in some cases with the reference drug tamoxifen and exhibiting a low cytotoxic effect against healthy cells. In silico molecular coupling studies at the tamoxifen binding site of ERα and GPER receptors revealed affinity and the possible mode of interaction of both compounds BTA-1 and BMZ-2.

scholarly journals Structurally Simple Phenanthridine Analogues Based on Nitidine and Their Antitumor Activities

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 437
Author(s):  
Shu-Qin Qin ◽  
Lian-Chun Li ◽  
Jing-Ru Song ◽  
Hai-Yun Li ◽  
Dian-Peng Li
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
A549 Cells ◽  
Anticancer Activities ◽  
Human Cancer Cell Lines ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Diphenyl Tetrazolium Bromide ◽  
Conjugated Compounds

A series of novel structurally simple analogues based on nitidine was designed and synthesized in search of potent anticancer agents. The antitumor activity against human cancer cell lines (HepG2, A549, NCI-H460, and CNE1) was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The results showed that some of them had good anticancer activities, especially derivatives with a [(dimethylamino)ethyl]amino side chain in the C-6 position. Planar conjugated compounds 15a, 15b, and 15c, with IC50 values of 1.20 μM, 1.87 μM, and 1.19 μM against CNE1 cells, respectively, were more active than nitidine chloride. Compound 15b and compound 15c with IC50 values of 1.19 μM and 1.37 μM against HepG2 cells and A549 cells demonstrated superior activities to nitidine. Besides, compound 5e which had a phenanthridinone core displayed extraordinary cytotoxicity against all test cells, particularly against CNE1 cells with the IC50 value of 1.13 μM.

Prothymosin α and Its C-Terminal Immunoreactive Decapeptide Show no Evidence of Acute Toxicity: A Preliminary in Silico, in Vitro and in Vivo Investigation

2021 ◽  
Vol 28 ◽  
Author(s):  
Anastasios I. Birmpilis ◽  
Panagiotis Vitsos ◽  
Ioannis V. Kostopoulos ◽  
Lillian Williams ◽  
Kyriaki Ioannou ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
In Silico ◽  
Human Cancer ◽  
Cell Cycle Distribution ◽  
Human Cancer Cell Lines ◽  
Prothymosin Α ◽  
High Concentrations ◽  
Immunocompetent Mice

Background: Members of the α-thymosin family have long been studied for their immunostimulating properties. Among them, the danger-associated molecular patterns (DAMPs) prothymosin α (proTα) and its C-terminal decapeptide proTα(100–109) have been shown to act as immunomodulators in vitro, due to their ability to promote T helper type 1 (Th1) responses. Recently, we verified these findings in vivo, showing that both proTα and proTα(100-109) enhance antitumor-reactive T cell-mediated responses. Methods: In view of the eventual use of proTα and proTα(100-109) in humans, we investigated their safety profile in silico, in human leukocytes and cancer cells lines in vitro, and in immunocompetent mice in vivo, in comparison to the proTα derivative thymosin alpha 1 (Τα1), a 28-mer peptide extensively studied for its safety in clinical trials. Results: In silico prediction via computational tools showed that all three peptide sequences likely are non-toxic or do not induce allergic regions. In vitro, proTα, proTα(100-109) and Tα1 did not affect the viability of human cancer cell lines and healthy donor-derived leukocytes, did not promote apoptosis or alter cell cycle distribution. Furthermore, mice injected with proTα, proTα(100-109) and Tα1 at doses equivalent to the suggested dose regimen of Tα1 in humans, did not show signs of acute toxicity, whereas proTα and proTα(100-109) increased the levels of proinflammatory and Th1-type cytokines in their peripheral blood. Conclusion: Our preliminary findings suggest that proTα and proTα(100-109), even at high concentrations, are non-toxic in vitro and in an acute toxicity model in vivo; moreover, we show that the two peptides retain their immunomodulatory properties in vivo and, eventually, could be considered for therapeutic use in humans.

scholarly journals In vitro and In silico Evaluation of Structurally Diverse Benzyl-pyrrolidine-3-ol Analogues as Apoptotic Agents via Caspase Activation

2021 ◽  
Vol 68 (3) ◽  
pp. 667-682
Author(s):  
Tahira Naqvi ◽  
Asif Amin ◽  
Shujat Ali ◽  
Mohsin Y. Lone ◽  
Nadeem Bashir ◽  
...  
Keyword(s):  
Cell Lines ◽  
In Silico ◽  
Caspase 3 ◽  
Human Cancer ◽  
Md Simulations ◽  
Human Cancer Cell Lines ◽  
Lead Compounds ◽  
Model Protein ◽  
The Stability

The activation of caspases is central to apoptotic process in living systems. Defects in apoptosis have been implicated with carcinogenesis. Need to develop smart agents capable of inducing apoptosis in tumor cells is obvious. With this motive, diversity oriented synthesis of 1-benzylpyrrolidin-3-ol analogues was envisaged. The multi component Ugi reaction synthesized library of electronically diverse analogues was explored for cytotoxic propensity towards a panel of human cancer cell lines at 10 μM. The lead compounds exhibit a selective cytotoxicity towards HL-60 cells as compared to cell lines derived from solid tumors. Besides, their milder cytotoxic effect on non-cancerous cell lines reaffirm their selective action towards cancer cells only.The lead molecules were tested for their ability to target caspase-3, as a vital protease triggering apoptosis. The lead compounds were observed to induce apoptosis in HL-60 cells around 10 μM concentration. The lead compounds exhibited various non-covalent supra type interactions with caspase-3 key residues around the active site. The binding ability of lead compounds with caspase-3 was studied via molecular docking and molecular dynamic (MD) simulations. MD simulations indicated the stability of compound-caspase-3 complex throughout the 50 ns simulation run. The stability and bio-availability of the lead compounds under physiological conditions was assessed by their interaction with Bovine Serum Albumin (BSA) as model protein. BSA interactions of lead compounds were studied by various bio-physical methods and further substantiated with in silico MD simulations.

scholarly journals Antioxidant Stress and Anticancer of Peptide Chelate Selenium Element in vitro

2020 ◽  
Author(s):  
Xian Li ◽  
Xianjue Wang ◽  
Gang Liu ◽  
Yanan Xu ◽  
Xinlin Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Photoelectron Spectroscopy ◽  
Human Cancer ◽  
Sulfhydryl Group ◽  
Ultraviolet Absorption Spectrum ◽  
Anticancer Activities ◽  
X Ray ◽  
Human Cancer Cell Lines

Abstract This contribution reports a facile synthesis of anticancer bioactive peptides (ACBP) - functionalized selenium particles (ACBP-S-Se) with enhanced anticancer activities and a detailed mechanistic evaluation of its regulation of oxidative stress in vitro. Structural and chemical characterizations were proved by ultraviolet absorption spectrum (UV), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Nuclear magnetic resonance carbon (13C NMR) and hydrogen spectra (H NMR), scanning electron microscope (SEM), energy dispersive X-ray spectrom (EDX) and inductively coupled plasma mass spectrometry (ICP-MS). The results show that ACBP are effectively sulfhydrylation modification with S-acetylmercaptosuccinic anhydride (SAMSA) via chemical absorption. After the polypeptide was modified by sulfhydrylation, there were many sulfhydryl groups on the molecule, and the sulfhydryl group was used as the binding site of Se. A panel of selected human cancer cell lines demonstrated high susceptibility toward ACBP-S-Se and displayed significantly reduced proliferative abilities. Finally, the results presented herein suggest bioactive peptide chelate selenium element effectively inhibited the proliferation of MKN-45 and MKN-74 cell in vitro, which in turns allowed the successful application of the ACBP-S-Se in highly complex human cell lines. The related the regulation of oxidative stress gene is CDKN1A, CCNB1, TXN and MAP3K5, while CDKN1A and TXN have ability to protecting cells to reduce oxidative stress and promoting cell growth arrest. Therefore, the great potential exhibited by ACBP-S-Se could make them an ideal candidate as a chemotherapeutic agent for human cancers, especially for gastric cancer.

scholarly journals Design, Synthesis, and Anticancer Activities of Novel 2-Amino-4-phenylthiazole Scaffold Containing Amide Moieties

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Zhi-Hua Zhang ◽  
Hong-Mei Wu ◽  
Sai-Nan Deng ◽  
Xiao-Yu Cai ◽  
Yu Yao ◽  
...  
Keyword(s):  
Cell Lines ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Structural Characteristics ◽  
Docking Study ◽  
Anticancer Activities ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines ◽  
Biological Studies

Appropriately substituted 2-amino-4-phenylthiazole derivatives were designed and synthesized according to the structural characteristics of crizotinib. The obtained compounds were characterized using 1H NMR, 13C NMR, and HRMS. The target compounds 5a–o were evaluated for their in vitro antiproliferative activity against A549, HeLa, HT29, and Karpas299 human cancer cell lines. Based on results of biological studies, some of these compounds exhibited significant antiproliferative activity. Compound 5b possessed outstanding growth inhibitory effects on the four cell lines, especially for HT29 cell with IC50 value of 2.01 µM. Along with the biological assay data, a molecular docking study suggests that the target compounds were a potential inhibitor.

Isolation, Solid-state Structure Determination, In Silico and In Vitro Anticancer Evaluation of an Indole Amino Acid Alkaloid L-Abrine

2019 ◽  
Vol 19 (9) ◽  
pp. 707-715
Author(s):  
Subrata Laskar ◽  
Omar Espino ◽  
Debasish Bandyopadhyay
Keyword(s):  
Solid State ◽  
In Silico ◽  
Human Cancer ◽  
Human Cancer Cell ◽  
State Structure ◽  
White Variety ◽  
X Ray ◽  
Human Cancer Cell Lines ◽  
Abrus Precatorius

Background: Abrus precatorius Linn. (Kunch in Bengali) is widely spread in tropical and sub-tropical regions. It is a typical plant species which is well-known simultaneously as folk medicine and for its toxicity. Objective: Phytoceutical investigation of the white variety seeds of Abrus precatorius Linn. Methods: Traditional extraction, separation, isolation, and purification processes were followed. The structure was elucidated by various spectral analyses and the solid-state structure of this indolealkaloid was determined by X-ray crystallographic analysis. Docking interactions of L-abrine had been studied against ten major proteins, responsible for various types of cancers. In silico studies were done by Schrödinger Maestro, AutoDock4, PyMOL and AutoDock Vina. The protein structures were downloaded from Protein Data Bank. Sulforhodamine B (SRB) colorimetric assay was used for in vitro anticancer evaluation against four human cancer cell lines. Results: An indole-containing unusual amino acid alkaloid had been isolated from the white variety seeds of Abrus precatorius Linn. In silico docking studies demonstrated significant antiproliferative activity against four human cancer cell lines. Conclusion: The solid-state zwitterion structure of the indole-containing alkaloid (α-methylamino- β-indolepropionic acid, L-abrine) has been confirmed for the first time by X-ray crystallography. Highly promising in silico and in vitro results indicate that L-abrine may find its space in future anticancer drug discovery research.

Synthesis and in vitro evaluation of naphthalimide–benzimidazole conjugates as potential antitumor agents

2019 ◽  
Vol 17 (21) ◽  
pp. 5349-5366 ◽  
Author(s):  
Iqubal Singh ◽  
Vijay Luxami ◽  
Kamaldeep Paul
Keyword(s):  
Biological Activity ◽  
Cell Lines ◽  
Antitumor Agents ◽  
Human Cancer ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Cancer Types ◽  
First Time ◽  
Potential Antitumor

A novel series of benzimidazole-naphthalimide conjugates was synthesized for the first time and screened for in vitro biological activity for 60 human cancer cell lines representing nine different cancer types.

scholarly journals Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4302
Author(s):  
Xiao-Long Sun ◽  
Mei-Lin Zhu ◽  
Yi-Qun Dai ◽  
Hong-Mei Li ◽  
Bo-Han Li ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Biological Activities ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Antitumor Effects ◽  
Concentration Dependent Manner ◽  
Human Cancer Cell Lines

Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 μM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.

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