Design, Synthesis, and Characterization of Novel Linomide Analogues and their Evaluation for Anticancer Activity

2020 ◽  
Vol 17 (2) ◽  
pp. 203-212
Author(s):  
Rudrax N.S. Priolkar ◽  
Sunil Shingade ◽  
Mahesh Palkar ◽  
Shivalingrao M. Desai
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Anticancer Agents ◽  
In Silico ◽  
Research Work ◽  
Chemotherapeutic Agents ◽  
Primary Amines ◽  
Tyrosine Kinase Domain ◽  
Compound Ii

Background: According to WHO, in 2017, about 90.5 million people suffered from cancer and about 8.8 million deaths occurred due to disease. Although the chemotherapeutic agents have decreased the mortality among the cancer patients but high toxicity and non-specific targets are still major drawbacks. : Many researchers have identified linomide, a 4-hydroxy-2-quinolone derivative, as a lead molecule for the development of anticancer agents. With this background, we thought of the following objective. Objective: The objective of this research work involves the synthesis of a series of N-(2-(4- hydroxy-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-2-oxoethyl)-N-alkyl substituted benzene sulfonamides IVa-d (1-3) by replacing the anilide moiety at the third position of linomide with sulfamoylacyl and also N-methyl by N-phenyl functionality. To perform in silico anticancer activity by using Molegro Virtual Docker (MVD-2013, 6.0) software and in vitro anticancer activity by MTT assay. Methods: The starting material 4-hydroxy-1-phenylquinolin-2(1H)-one was treated with N-bromosuccinamide to yield compound II. Condensation of compound II with primary amines resulted in compounds IIIa-d, which, on coupling with substituted aromatic sulfonyl chlorides yield the title compounds IVa-d (1-3). Results: All the synthesized compounds were satisfactorily characterized by spectral data. The results of docking revealed that the synthesized compounds exhibited well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of EGFRK tyrosine kinase domain (PDB ID: 1m17). The MolDock Score of compound IVd-1 (-115.503) was the highest amongst those tested. The in vitro anticancer activity results showed that compound IVc-1 (R= - (CH2) 2-CH3 ; R′= -H) and IV d-1 (R= -CH2-C6H5; R′= -H) were found to be most potent against K562 cell line with an IC50 of 0.451 μM/ml and 0.455 μM/ml respectively. Compound IVd-1 also showed better potency against A549 cell line with IC50 value of 0.704 μM/ml. Conclusion: The results of in silico and in vitro anticancer activity are in agreement with each other. Compound IV d-1 was found to be most active of the series.

Design, Synthesis, In vitro and In silico Evaluation of New Hydrazonebased Antitumor Agents as Potent Akt Inhibitors

2020 ◽  
Vol 17 (11) ◽  
pp. 1380-1392
Author(s):  
Emine Merve Güngör ◽  
Mehlika Dilek Altıntop ◽  
Belgin Sever ◽  
Gülşen Akalın Çiftçi
Keyword(s):  
Cell Line ◽  
Anticancer Agents ◽  
In Silico ◽  
Antitumor Agents ◽  
Colorimetric Assay ◽  
Fibroblast Cell ◽  
Lipinski’S Rule ◽  
In Silico Docking ◽  
Embryonic Fibroblast

Background: Akt is overexpressed or activated in a variety of human cancers, including gliomas, lung, breast, ovarian, gastric and pancreatic carcinomas. Akt inhibition leads to the induction of apoptosis and inhibition of tumor growth and therefore extensive efforts have been devoted to the discovery of potent antitumor drugs targeting Akt. Objectives: The objective of this work was to identify potent anticancer agents targeting Akt. Methods: New hydrazone derivatives were synthesized and investigated for their cytotoxic effects on 5RP7 H-ras oncogene transformed rat embryonic fibroblast and L929 mouse embryonic fibroblast cell lines. Besides, the apoptotic effects of the most active compounds on 5RP7 cell line were evaluated using flow cytometry. Their Akt inhibitory effects were also investigated using a colorimetric assay. In silico docking and Absorption, Distribution, Metabolism and Excretion (ADME) studies were also performed using Schrödinger’s Maestro molecular modeling package. Results and Discussion: Compounds 3a, 3d, 3g and 3j were found to be effective on 5RP7 cells (with IC50 values of <0.97, <0.97, 1.13±0.06 and <0.97 μg/mL, respectively) when compared with cisplatin (IC50= 1.87±0.15 μg/mL). It was determined that these four compounds significantly induced apoptosis in 5RP7 cell line. Among them, N'-benzylidene-2-[(4-(4-methoxyphenyl)pyrimidin- 2-yl)thio]acetohydrazide (3g) significantly inhibited Akt (IC50= 0.5±0.08 μg/mL) when compared with GSK690693 (IC50= 0.6±0.05 μg/mL). Docking studies suggested that compound 3g showed good affinity to the active site of Akt (PDB code: 2JDO). According to in silico ADME studies, the compound also complies with Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 3g stands out as a potential orally bioavailable cytotoxic agent and apoptosis inducer targeting Akt.

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Microwave Assisted Synthesis ◽  
Binding Affinities ◽  
In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

SYNTHESIS, SPECTRAL CHARACTERIZATION AND ANTICANCER EVALUATION OF NEW DIAZENYL SCHIFF BASE DERIVATIVES

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (02) ◽  
pp. 20-28
Author(s):  
P. K. N. Sarangi ◽  
◽  
J. Sahoo ◽  
S. K Paidesetty ◽  
G. P. Mohanta
Keyword(s):  
Schiff Base ◽  
Anticancer Activity ◽  
Cell Line ◽  
Leukemia Cell ◽  
Cancer Cell Line ◽  
Leukemia Cell Line ◽  
Primary Amines ◽  
Schiff Base Derivatives ◽  
Mcf 7

A series of several diazenyl Schiff base derivatives were designed and synthesized through azo coupling of diazotised primary amines with the novel synthesized Schiff base ligand (E)-N-((2-chloroquinolin-3-yl) methylene)-4-phenylthiazol-2-amine. All the synthesized compounds have been analysed by different spectral techniques such as elemental analysis, 1H NMR, FT-IR, UV-Vis and LC-MS for their structural confirmation. The above conjugates have been studied for their solvent effects by treating them with different solvents. The results of in vitro cytotoxic study of the synthesized compounds against MCF 7 (human breast cancer cell line) and K562 (Chronic Myeloid Leukemia cell line) revealed that some of the compounds show cytotoxic effect. However, the compounds (NZ)-N-(((4-bromo-3-methylphenyl) diazenyl) (2-chloroquinolin-3-yl) methylene)-4-phenylthiazol-2-amine: (5d) and 4-(((Z)-(2-chloroquinolin-3- yl)(4-phenylthiazol-2-ylimino)methyl)diazenyl)phenol (5e) showed potent cytotoxic activity in comparison to other compounds against MCF 7. Corroborating the results of anticancer activity, it is found to be observed that the compound 4- (((Z)- (2-chloroquinolin-3-yl) (4-phenylthiazol-2-ylimino)methyl) diazenyl) phenol (5e) showed excellent anticancer activity against MCF 7, which is further justified by the apoptosis study through Annexin V-FITC/PI analysis.

IN SILICO CHARACTERIZATION, MOLECULAR DOCKING, AND IN VITRO EVALUATION OF TRIAZOLE DERIVATIVES AS POTENTIAL ANTICANCER AGENTS

2021 ◽  
pp. 22-28
Author(s):  
HARSHITHA T ◽  
VINAY KUMAR T ◽  
VINEETHA T
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Docking Studies ◽  
Pharmacokinetic Parameters ◽  
Pancreatic Cell ◽  
Triazole Derivatives ◽  
Wet Lab

Objective: The objective of the study was to perform in silico molecular docking and in vitro anticancer studies of proposed 1,2,4-triazole derivatives for the determination of their anticancer activity. Methods: A series of 10 triazole compounds with different substituents were drawn in ACD Lab ChemSketch software. Molecular and biological properties were identified using Molinspiration software. The compounds that obeyed Lipinski rule of five are subjected for pharmacokinetic parameters prediction and docking analysis. SwissDock ADME software is used for the prediction of absorption, distribution, metabolism, and elimination. Then, the compounds are docked with target enzymes in Chimera software 1.14 version. The molecular docking studies revealed favorable molecular interactions and binding energies. The compounds that showed good docking results were synthesized through wet lab synthesis and further preceded for in vitro anticancer studies. Results: Three compounds are selected for wet lab synthesis due to their good docking results compared to other compounds. The synthesized compounds are subjected to different in vitro anticancer studies and found to be having potential anticancer activity. Conclusion: The pharmacokinetic and docking studies conclude that the triazole compounds have potential as anticancer agents. The in vitro anticancer studies revealed that the triazole derivatives are having high potency of anticancer activity against pancreatic cell lines.

Design, Synthesis of novel coumarin conjugated acetamides as promising anticancer agents: An in-silico and in-vitro approach.

2020 ◽  
Vol 20 ◽  
Author(s):  
Mamatha S. V ◽  
S. L. Belagali ◽  
Mahesh Bhat ◽  
Vijay M. Kumbar
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Mtt Assay ◽  
Anticancer Agents ◽  
In Silico ◽  
Active Sites ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Mcf 7

Background: Coumarin and benzophenone possess a vast sphere of biological activities whereas thiazoles display various pharmacological properties. Hence we focused on incorporation of coumarin and thiazole core to the benzophenone skeleton to enhance the bioactivity anticipating their interesting biological properties. Objective: The objective of the current work is synthesis and biological evaluation of a novel series of coumarin fused thiazole derivatives. Methods: A novel series of Coumarin conjugated thiazolyl acetamide hybrid derivatives were synthesized by multistep reaction sequence and were characterized by the FT-IR, LCMS and NMR spectral techniques. The newly synthesized compounds were screened for anticancer activity by in-silico and in-vitro methods. The cytotoxicity of the synthesized unique compounds had been executed for two different cancer cell lines MCF-7 (Breast cancer) and KB (Oral cancer) in comparison with standard paclitaxel by MTT assay. Results: The compound 7f is the potent motif with an acceptable range of IC 50 values for anticancer activity were 63.54 µg/ml and 55.67 µg/ml, against the MCF-7 and KB cell lines, respectively. Molecule docking model revealed that this compound formed three conventional hydrogen bonds with the active sites of the amino acids MET 769, ARG 817 and LYS 721. Conclusion: Compound 7f with two methyl groups on the phenoxy ring and one 4-position methoxy group on the benzoyl ring, showed a significant cytotoxic effect. An advantageous level of low toxicity against normal cell line (L292) by MTT assay was determined.

Anticancer Evaluation and Docking Study of New Bifunctional Phthalazine Derivatives

2018 ◽  
Vol 15 (3) ◽  
pp. 414-422 ◽  
Author(s):  
Marwa G. El-Gazzar ◽  
Hala M. Aly
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Anticancer Agents ◽  
Active Site ◽  
Cancer Cell Line ◽  
Docking Study ◽  
Quinazoline Derivative ◽  
Spectroscopic Measurements ◽  
Ic50 Value

Aims and Objective: A series of novel phthalazine derivatives was synthesized with versatile, readily accessible electrophilic and nucleophilic reagents. The newly synthesized compounds were confirmed by the results of spectroscopic measurements. Hence, their potential clinical application investigated in particular for cancer treatment. Materials and Methods: The newly synthesized compounds were characterized by spectroscopic measurements and were tested for their in vitro anticancer activity by MTT assay against human liver cancer cell line. Docking study of all the synthesized compounds was performed within the active site of the enzyme VEGFR-2 (Vascular Endothelial Growth Factor Receptor-2). Results: The quinazoline derivative 12 emerged as the most potent compound in this study with an IC50 value of 5.4 µM. Docking study showed that the synthesized compounds were fit in the VEGFR-2 active site almost at the same position of sorafenib and vatalanib with comparable docking scores (-15.20 to -8.92 was kcal/mol). Conclusion: we have synthesized a novel series of phthalazine derivatives and evaluated their potential anticancer activity against HEPG2 cell line. The quinazoline derivative 12 emerged as the most potent compound in this study with an IC50 value of 5.4 µM. The SAR and docking studies pointed out that rigidification of the structure resulted in better activity and better binding within the active site of VEGFR-2 as in compounds 3, 5, 6 and 12. These results introduced new phthalazine derivatives having promising activity which could lead to the development of more potent anticancer agents.

scholarly journals An in silico evaluation of CDK Inhibitors targeting BCL2, TS and mTOR

2021 ◽  
Vol 7 (2) ◽  
pp. 126-131
Author(s):  
Sharmin Ahmed Rakhi ◽  
Muhammad Asaduzzaman ◽  
Nishat Nasin ◽  
Abul Bashar Mir Md Khademul Islam
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
In Silico ◽  
Target Therapy ◽  
Research Work ◽  
Chemotherapeutic Agents ◽  
Physical Interaction ◽  
Cdk Inhibitors ◽  
Molecular Docking Study ◽  
Human Cancers

The cyclin dependent kinase (CDK) inhibitors have recently been found to be of potential use as anticancer drugs. The present research work focuses on screening of compounds targeting multiple pathways involved in human cancers along with CDK-regulated cell cycle for prospective anticancer potential. Molecular docking study of selected compounds were performed to determine the binding affinity of selected compounds towards respective targets of cancer cells to verify if there is any physical interaction of these inhibitors with their reported target proteins as claimed in the existing literatures. Prior to docking, molecular pathway prediction and gene set enrichment analyses were performed to identify the target molecules by using appropriate bioinformatics tools. Interestingly, the results of in silico molecular docking have been found to be in line with the laboratory findings that are obtained from the literatures. Specifically, few of our selected CDK inhibitors, namely Abemaciclib, Palbociclib, AMG 925 and RGB 286638 showed good binding scores against BCL2, TS, mTOR in addition to CDKs (4, 6 and 9). On the basis of scientific evidence based on published scholarly articles and according to molecular docking results, it can be inferred that these CDK inhibitors as anticancer agents may play a very promising role in cancer treatment and can be used as potential lead compounds for the development of target therapy against human cancers. However, more intensive research is needed to confirm the feasibility of these compounds to be used in treating cancer and it is expected that this work will provide a stimulating impetus for the development of chemotherapeutic agents in future. Asian J. Med. Biol. Res. 2021, 7 (2), 126-131

scholarly journals In vitro Anticancer Activity of Marine Sponges Against T47D and HeLa Cell Lines

2020 ◽  
Vol 19 (1) ◽  
pp. 25-28
Author(s):  
Suciati ◽  
Lusiana Arifianti
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Marine Sponges ◽  
Hela Cell Lines

Marine sponges have been known as the source of natural products. Various metabolites with potent bioactivities have been reported from this organism. The current study aims to investigate the anticancer potency of three marine sponges namely Diacarnus debeauforti, Haliclona amboinensis and Agelas cavernosa collected from Barrang Lompo Island, South Sulawesi, Indonesia. The ethyl acetate extracts of the sponges were screened against T47D breast cancer cells and HeLa cervical cancer cells by using the MTT method. The results showed that these sponges demonstrated anticancer activity against both cancer cell lines. The lowest IC50 of 18.2 μg/ml was given by the extract of A. cavernosa against T47D cell line, while in the screening against HeLa cancer cell line, the extract of D. debeauforti revealed the highest potency with IC50 of 15.7 μg/ml. Our results suggested that the marine sponges namely D. debeauforti, H. amboinensis and A. cavernosa can be good candidates for the development of anticancer agents. Dhaka Univ. J. Pharm. Sci. 19(1): 25-28, 2020 (June)

In vitro and in silico anticancer activity of amygdalin on the SK-BR-3 human breast cancer cell line

2019 ◽  
Vol 46 (6) ◽  
pp. 6361-6370 ◽  
Author(s):  
Bahman Moradipoodeh ◽  
Mostafa Jamalan ◽  
Majid Zeinali ◽  
Masood Fereidoonnezhad ◽  
Ghorban Mohammadzadeh
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Cell Line ◽  
Breast Cancer Cell Line ◽  
In Silico ◽  
Human Breast Cancer ◽  
Cancer Cell Line ◽  
Human Breast Cancer Cell ◽  
Human Breast

scholarly journals Synthesis and Characterization of 2-Phenylpyrazoline Derivatives and Evaluation of their Activities against Antimicrobial and Breast Cancer Cell Line in vitro and in silico Studies

2019 ◽  
Vol 31 (6) ◽  
pp. 1311-1320
Author(s):  
RAJA CHINNAMANAYAKAR ◽  
M.R. EZHILARASI
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Cell Line ◽  
Mtt Assay ◽  
In Silico ◽  
Assay Method ◽  
Zone Of Inhibition ◽  
Binding Interaction ◽  
In Silico Studies

The new series of 2-phenylpyrazoline derivatives (2a-j) were synthesized and evaluated for their antimicrobial, in silico and in vitro anticancer activity was performed by MTT assay using MDA-MB-231 (human breast adenocarcinoma) cell line. The 2-phenylpyrazoline derivatives (2a-j) were obtained by the cyclization of chalcones with phenylhydrazine hydrochloride. Synthesized compounds were confirmed using FT-IR, 1H NMR and 13C NMR spectral data. Molecular docking studies were carried out using Auto Dock Tool version 1.5.6 and Auto dock version 4.2.5.1 docking program. in silico Docking study, compound 2d showed good binding score and good binding interaction with selected bacterial proteins and breast cancer protein. Based on this result, compound 2d was performed the anticancer activity by MTT assay method. From this result, compound 2d shown the LC50 value is 185.30 ± 1. 469 μg/mL. From the antibacterial activity compound 2i (2,3-dichloro substituted 2-pyrazoline derivative) showed a good zone of inhibition at high concentration (100 mg/mL) as compared to other derivatives (2a-j) and compound 2c (fluoro substituted 2-phenylpyrazoline derivative) showed a good zone of inhibition at low concentration (25 mg/mL) compared to other derivative (2a-j).

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