DESIGN, SYNTHESIS AND EVALUATION OF 6-SUBSTITUTED-4-HYDROXY-1-(2- SUBSTITUTEDACETYL)-3-NITROQUINOLIN-2(1H)-ONES FOR ANTICANCER ACTIVITY

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (12) ◽  
pp. 20-27
Author(s):  
S. S Bhat ◽  
◽  
S. N. MamleDesai ◽  
V. Narvekar ◽  
S. G Shingade ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Docking Study ◽  
The Other ◽  
Secondary Amines ◽  
Chloroacetyl Chloride ◽  
Design Synthesis ◽  
Mass Spectral ◽  
Ic50 Values ◽  
Substituted 1

The present work deals with the synthesis of a series of 6-substituted-4-hydroxy-1-(2-substitued alicyclicaminoacetyl)-3-nitroquinolin-2(1H)-one {IVa-d (1-3)} derivatives and evaluation of their in vitro anticancer activity. Docking study was carried out using EGFR-tyrosine kinase binding site (PDB ID: 1m17) and revealed encouraging results. The sequence of reactions consists of the initial synthesis of 6-substituted 4-hydroxyquinolin-2(1H)-ones (Ia-d), which were further subjected to nitration reaction to give 6- substituted-4-hydroxy-3-nitroquinolin-2(1H)-one (IIa-d). Condensation of compounds (IIa-d) with chloroacetyl chloride resulted in 6-substituted-1-(2-chloroacetyl)-4-hydroxy-3-nitroquinolin-2(1H)-one(IIIa-d), which was subjected to substitution reaction using various secondary amines to yield the title compounds {IVa-d (1-3)}. All the synthesized compounds were characterized by IR, NMR and mass spectral data.All the derivatives were tested for their in vitro anticancer activity using KB (oral cancer) cell lines. Among the synthesized compounds, compound (IVc-2) was found to be the most cytotoxic as compared to the other synthesized derivatives, with IC50 values of 0.2406μM/mL against KB cell line.

scholarly journals DESIGN, SYNTHESIS AND COX1/2 INHIBITORY ACTIVITY OF NEW QUINAZOLINE-5-ONE DERIVATIVES

2017 ◽  
Vol 13 (1) ◽  
pp. 5923-5931
Author(s):  
Ahmed S. Aboraia ◽  
Mohammed A. Hara ◽  
Mostafa H. Abdelrahman ◽  
Mohamed M. Amin ◽  
Osama I. El-Sabbaghab
Keyword(s):  
Active Site ◽  
Docking Study ◽  
Selectivity Index ◽  
Inhibition Assay ◽  
Inhibitor Concentration ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Cox 2 ◽  
Cox 1

A new series of 1-(4-Acetylphenyl)-7,7-dimethyl-3-(substitutedphenyl)-1,2,3,4,7,8-octahydroquinazolin-5(6H)-ones (6-15) were synthesized and tested against COX-1 and COX-2 enzymes. Those compounds exhibited strong interaction at the COX-2 binding site and poor interaction at the COX-1 active site. Subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assay; most of the compounds especially compounds 6, 7, 12, 13, and 16 exhibited potent anti-inflammatory effects, selective COX-2 inhibition, with half-maximal inhibitor concentration (IC50) values of 0.22–1.42 μM and selectivity index (SI) values of 6.16–14.18 compared with celecoxib (IC50 = 0.05 μM and COX-2 SI: 296), diclofenac (IC50 = 0.8 μM and COX-2 SI: 4.87), and indomethacin (IC50 = 0.49 μM and COX-2 SI: 0.08) as reference drugs. Docking study has been carried out to confirm the binding affinity and selectivity of the most active compound (compound 6) to COX-2 enzyme.

scholarly journals Design, Synthesis and Characterization of Novel Amine Derivatives of 5-[5-(Chloromethyl)-1, 3, 4-Oxadiazol-2-yl]- 2-(4-Fluorophenyl)-Pyridine as a New Class of Anticancer Agents

2017 ◽  
Vol 16 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Adimule Vinayak ◽  
Medapa Sudha ◽  
Kumar S Lalita
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Secondary Amines ◽  
Design Synthesis ◽  
Human Cancer Cell Lines ◽  
Ic50 Values ◽  
High Cytotoxicity ◽  
Hepg2 Cell Lines

A linear strategy was adopted in synthesizing the novel amine derivatives 7(a-h) of 5-[5- (chloromethyl)-1, 3, 4-oxadiazol-2-yl]-2-(4-fluorophenyl)-pyridine (6) and screened these compounds for in vitro anticancer activity against three human cancer cell lines (HeLa,Caco-2 and HepG2). The synthesised novel compounds were characterized by 1H NMR, MS and 13C NMR spectroscopic evidences. Microwave irradiation of compound (5) in presence of chloroacetyl chloride and phosphoryl oxychloride yielded the dehydrated cyclized key intermediate 5-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]-2-(4-fluorophenyl)-pyridine which upon treatment with various primary or secondary amines (a-h) resulted into the corresponding amine derivatives. The IC50 values of the final compounds were compared with that of 5-fluorouracil (5-FU) taken as the standard. Compounds 7a and 7d were found to be highly cytotoxic against HepG2 cell lines with IC50 values of 2.6 ?M (IC50 = 34.0 ± 0.5 ?M) and 5.8 ?M (IC50 = 112 ± 1.4 ?M) respectively. The compound (7f) alone was found to have high cytotoxicity against Caco-2 cell lines with IC50 value of 2.3 ?M (IC50 = 87 ± 2.6 ?M).Dhaka Univ. J. Pharm. Sci. 16(1): 11-19, 2017 (June)

scholarly journals SYNTHESIS, CHARACTERIZATION, AND ANTICANCER ACTIVITY OF SOME NOVEL ACRIDINE DERIVATIVES

2020 ◽  
pp. 166-169
Author(s):  
SWETHA PADIGELA ◽  
BHAGAVAN RAJU RM ◽  
RAJENDRA PRASAD VVS
Keyword(s):  
Spectral Analysis ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Mtt Assay ◽  
Chloroacetyl Chloride ◽  
Mass Spectral Analysis ◽  
Mass Spectral ◽  
Acridine Derivatives ◽  
Mcf 7

Objective: The objective of the study was to synthesize and evaluate the anticancer activity of some novel acridine derivatives. Methods: The present works involve condensation of acridine and various 2, 4-Thiazolidine-2,4-dione derivatives (2a–2h) with chloroacetyl chloride to give a novel acridine derivatives (5a–5l), respectively. Results: All the newly synthesized molecules (5a–5l) were characterized by FTIR, H1-NMR, and mass spectral analysis along with physical data. The biological potentials of the new synthesized compounds are evaluated for their in vitro anticancer activity by MTT assay. Conclusion: The synthesized compounds 5a, 5f, and 5h exhibited good anticancer activity against MCF-7 and SKVO3 cancer cell lines at a concentration of 0.5 mg/mL-1.

scholarly journals Design, Synthesis and Preliminary Biological Evaluation of Benzylsulfone Coumarin Derivatives as Anti-Cancer Agents

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4034 ◽  
Author(s):  
Tao Wang ◽  
Tao Peng ◽  
Xiaoxue Wen ◽  
Gang Wang ◽  
Yunbo Sun ◽  
...  
Keyword(s):  
Cell Lines ◽  
Docking Study ◽  
Biological Evaluation ◽  
Coumarin Derivatives ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Kinase Inhibitory Activity ◽  
In Silico Molecular Docking

In this work, a series of benzylsulfone coumarin derivatives 5a–5o were synthesized and characterized. Kinase inhibitory activity assay indicated that most of the compounds showed considerable activity against PI3K. Anti-tumor activity studies of the active compounds were also carried out in vitro on the Hela, HepG2, H1299, HCT-116, and MCF-7 tumor cell lines by MTS assay. The structure–activity relationships (SARs) of these compounds were analyzed in detail. Compound 5h exhibited the most potent activities against the mentioned cell lines with IC50 values ranging from 18.12 to 32.60 μM, followed by 5m with IC50 values of 29.30–42.14 μM. Furthermore, 5h and 5m clearly retarded the migration of Hela cells in vitro. Next, an in silico molecular docking study was conducted to evaluate the binding models of 5h and 5m towards PI3Kα and PI3Kβ. Collectively, the above findings suggested that compounds 5h and 5m might be promising PI3K inhibitors deserving further investigation for cancer treatment.

scholarly journals Design, Synthesis and in vitro Anticancer Evaluation of New 2H-benzo[b][1,4]thiazin-3(4H)-one Based 1,2,3-Triazoles

2019 ◽  
Vol 31 (11) ◽  
pp. 2647-2652 ◽  
Author(s):  
O. Rajender ◽  
S. Narsimha ◽  
N. Vasudeva Reddy
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Broad Spectrum ◽  
Moderate Activity ◽  
Design Synthesis ◽  
Triazole Derivatives ◽  
Cuaac Reaction ◽  
Ic50 Values ◽  
Mcf 7

A series of novel 2H-benzo[b][1,4]thiazin-3(4H)-one derived from 1,4-disubstituted 1,2,3-triazole derivatives (4a-j and 5a-j) were synthesized using Cu(I) catalyzed azide alkyne cyclization (CuAAC) reaction of the compounds 2 and 3 with various aromatic azides. The examination of in vitro anticancer activity revealed that the compounds 4d and 5d were found to possess a broad spectrum of anticancer activity against three cell lines MCF-7, HeLa and IMR-32 with IC50 values ranging from 26.28 ± 1.5 to 32.06 ± 0.3 M mL-1, respectively. The remaining compounds have shown good to moderate activity against the tested cell lines.

scholarly journals Design, Synthesis, and Anticancer Screening for Repurposed Pyrazolo[3,4-d]pyrimidine Derivatives on Four Mammalian Cancer Cell Lines

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2961
Author(s):  
Eman M. Othman ◽  
Amany A. Bekhit ◽  
Mohamed A. Anany ◽  
Thomas Dandekar ◽  
Hanan M. Ragab ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Anticancer Activity ◽  
Cell Lines ◽  
A549 Cells ◽  
Design Synthesis ◽  
In Silico Docking ◽  
Hela Cell Lines ◽  
Ic50 Values ◽  
High Cytotoxic Activity

The present study reports the synthesis of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to mono-, di-, and trimethoxy benzylidene moieties through hydrazine linkages. First, in silico docking experiments of the synthesized compounds against Bax, Bcl-2, Caspase-3, Ki67, p21, and p53 were performed in a trial to rationalize the observed cytotoxic activity for the tested compounds. The anticancer activity of these compounds was evaluated in vitro against Caco-2, A549, HT1080, and Hela cell lines. Results revealed that two (5 and 7) of the three synthesized compounds (5, 6, and 7) showed high cytotoxic activity against all tested cell lines with IC50 values in the micro molar concentration. Our in vitro results show that there is no significant apoptotic effect for the treatment with the experimental compounds on the viability of cells against A549 cells. Ki67 expression was found to decrease significantly following the treatment of cells with the most promising candidate: drug 7. The overall results indicate that these pyrazolopyrimidine derivatives possess anticancer activity at varying doses. The suggested mechanism of action involves the inhibition of the proliferation of cancer cells.

Synthesis, Antimalarial Evaluation and SAR Study of Some 1,3,5-Trisubstituted Pyrazoline Derivatives

2019 ◽  
Vol 16 (10) ◽  
pp. 807-817 ◽  
Author(s):  
Shilpy Aggarwal ◽  
Deepika Paliwal ◽  
Dhirender Kaushik ◽  
Girish Kumar Gupta ◽  
Ajay Kumar
Keyword(s):  
Antimalarial Activity ◽  
Analysis Data ◽  
Docking Study ◽  
Maximum Activity ◽  
Elemental Analysis Data ◽  
Mass Spectral ◽  
Structure Activity ◽  
Pharmacokinetic Properties ◽  
Sar Study

The synthesis of a novel series of 1,3,5-trisubstitiuted pyrazoline was achieved by refluxing chalcone derivative with different heteroaryl hydrazines. The newly synthesized compounds were characterized by 1H NMR, 13CNMR, mass spectral and elemental analysis data. The synthetic series of novel pyrazoline hybrids was screened for in vitro schizont maturation assay against chloroquine sensitive 3D7 strain of Plasmodium falciparum. Most of the compounds showed promising in vitro antimalarial activity against CQ sensitive strain. The preliminary structure-activity relationship study showed that quinoline substituted analog at position N-1 showed maximum activity followed by benzothiazole substitution, while phenyl substitution lowers the antimalarial activity. The observed activity was persistent by the docking study on P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction.

Novel coumarin containing dithiocarbamate derivatives as potent α-glucosidase inhibitors for management of type 2 diabetes

2020 ◽  
Vol 16 ◽  
Author(s):  
Marjan Mollazadeh ◽  
Maryam Mohammadi-Khanaposhtani ◽  
Yousef Valizadeh ◽  
Afsaneh Zonouzi ◽  
Mohammad Ali Faramarzi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kinetic Study ◽  
Active Site ◽  
Docking Study ◽  
Secondary Amines ◽  
Molecular Docking Study ◽  
Glucosidase Inhibitors ◽  
Dithiocarbamate Derivatives

Background: α-Glucosidase is a hydrolyze enzyme that plays a crucial role in degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in the carbohydrate mediated diseases such as diabetes mellitus. Objective: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico. Methods: These compounds were obtained of reaction between 4-(bromomethyl)-7-methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6). Results: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 μM) in comparison to acarbose as standard inhibitor (IC50 = 750.0 ± 9.0 µM). Among them, secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound compete with substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Also, molecular docking study predicted that this compound as well interacted with α-glucosidase active site pocket. Conclusion: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for design potent α-glucosidase inhibitors for treatment of type 2 diabetes.

Synthesis, SAR, In-Silico appraisal and Anti-Microbial Study of substituted 2-aminobenzothiazoles derivatives

2019 ◽  
Vol 15 ◽  
Author(s):  
Devidas G. Anuse ◽  
Suraj N. Mali ◽  
Bapu R. Thorat ◽  
Ramesh S. Yamgar ◽  
Hemchandra K. Chaudhari
Keyword(s):  
Antimicrobial Activity ◽  
In Silico ◽  
Docking Study ◽  
Moderate Activity ◽  
Molecular Docking Study ◽  
Mass Spectral ◽  
Gram Positive Bacteria ◽  
Ft Ir ◽  
In Silico Molecular Docking

Background: Antimicrobial resistance is major global health problem, which is being rapidly deteriorating the quality of human health. Series of substituted N-(benzo[d]thiazol-2-yl)-2-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)acetamide (3a-j) were synthesized from substituted N-(benzo[d]thiazol-2-yl)-2-chloroacetamide/bromopropanamide (2a-j) and 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (2) and further evaluated for their docking properties and antimicrobial activity. Methods: All synthesized compounds were characterized by FT-IR, NMR and Mass spectral analysis. All compounds were allowed to dock against different antimicrobial targets having PDB ID: 1D7U and against common antifungal target having PDB ID: 1EA1. Results: The compounds 3d and 3h were showed good activity against Methicillin-resistant Staphylococcus aureus (MRSA, resistance Gram-positive bacteria). All synthesized compounds showed good to moderate activity against selected bacterial and fungal microbial strains. If we compared the actual in-vitro antimicrobial activity and in-silico molecular docking study, we found that molecules 3i and 3h were more potent than the others. Conclusion: Our current study would definitely pave the new way towards designing and synthesis of more potent 2-aminobenzothiazoles derivatives.

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