Synthesis, Antiproliferative Activity and Molecular Docking of New Thiazole/Benzothiazole Fused Pyranopyrimidine Derivatives

2020 ◽  
Vol 17 (12) ◽  
pp. 951-958
Author(s):  
Pallava Nagaraju ◽  
Pedavenkatagari Narayana Reddy ◽  
Pannala Padmaja ◽  
Vinod G. Ugale
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Antiproliferative Activity ◽  
Aromatic Aldehydes ◽  
Human Colon ◽  
Docking Studies ◽  
Human Colon Cancer ◽  
One Pot ◽  
Human Embryonic Kidney Cells ◽  
Heterocyclic Molecules

A new class of 4H,5H-benzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidin-5-one and 5H,6Hpyrano[ 2,3-d]thiazolo[3,2-a]pyrimidin-5-one derivatives were synthesized via the one-pot threecomponent reaction of 2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one and 7-hydroxy-5Hthiazolo[ 3,2-a]pyrimidin-5-one to various aromatic aldehydes and malononitrile. This domino transformation involves the formation of pyranopyrimidine ring by the formation of three C–C bonds and one C– O bond a single synthetic operation. As the products precipitate out of the reaction, simple filtration is enough to gather the products, and thus, there is no need for work-up or column-chromatography. The synthesized thiazole/benzothiazole fused pyranopyrimidine derivatives were evaluated for their antiproliferative activity against four cancer cell lines namely DU 145 (prostate cancer), Hela (Human cervical cancer), MDA-MB-231 (breast cancer), HT-29 (Human colon cancer) and normal cell line HEK293 (human embryonic kidney cells). The results demonstrated that synthesized compounds were selective in its cytotoxicity to cancer cells compared to normal cells. Among these compounds, 2-amino-9- methoxy-5-oxo-4-(3,4,5-trimethoxyphenyl)-4H,5H-benzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidine- 3-carbonitrile 4i exhibited the most potent antiproliferative activity against the tested cell lines. Molecular docking studies revealed that these active heterocyclic molecules bind selectively in the colchicine binding site of tubulin polymer.

Microwave assisted synthesis of thiazole/benzothiazole fused pyranopyrimidine derivatives and evaluation of their biological activity

2020 ◽  
Vol 17 ◽  
Author(s):  
Pallava Nagaraju ◽  
Pedavenkatagari Narayana Reddy ◽  
Pannala Padmaja ◽  
Vinod G. Ugale
Keyword(s):  
Cell Lines ◽  
Antiproliferative Activity ◽  
Aromatic Aldehydes ◽  
Hek293 Cells ◽  
Microwave Assisted Synthesis ◽  
Human Colon Cancer ◽  
One Pot ◽  
Human Embryonic Kidney Cells ◽  
Heterocyclic Molecules ◽  
Three Component Reaction

: A new class of phenylbenzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidin-5-one and pyrano[2,3-d]thiazolo[3,2-a]pyrimidine-5-one derivatives have been synthesized via one pot three-component reaction of 2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one and 7- hydroxy-5H-thiazolo[3,2-a]pyrimidin-5-one with various aromatic aldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine under microwave irradiation. This transformation involves formation of thiazole or benzothiazole fused pyranopyrimidinone ring by creation of two C–C bonds and one C–O bond in a single synthetic operation. This rapid one-pot reaction does not require a catalyst, it is solvent-free, avoids chromatographic purification, and provides good yields. The synthesized compounds were evaluated for their antiproliferative activity against four cancer cell lines namely DU 145 (prostate cancer), MDA-MB-231 (breast cancer), Hela (Human cervical cancer), HT-29 (Human colon cancer) and HEK293 (human embryonic kidney cells). The results clearly demonstrated that synthesized compounds were selective in its cytotoxicity to cancer cells compared to normal HEK293 cells. Compound 12h exhibited the most potent antriproliferative activity against the tested cell lines, while other test compounds showed weak or moderate antiproliferative activity, among them 12d, 12e and 14d displayed showed IC50 values in the low micromolar range. Molecular docking studies revealed that these active heterocyclic molecules bind selectively in the colchicine binding site of tubulin polymer.

In vitro antiproliferative activity against human colon cancer cell lines of representative 4-thiazolidinones. Part I

2005 ◽  
Vol 15 (17) ◽  
pp. 3930-3933 ◽  
Author(s):  
Rosaria Ottanà ◽  
Stefania Carotti ◽  
Rosanna Maccari ◽  
Ida Landini ◽  
Giuseppa Chiricosta ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Human Colon ◽  
Colon Cancer Cell ◽  
Human Colon Cancer Cell ◽  
Human Colon Cancer ◽  
Colon Cancer Cell Lines

scholarly journals Synthesis of Novel 1,2,4-Triazolyl Coumarin Derivatives as Potential Anticancer Agents

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Lamya H. Al-Wahaibi ◽  
Hanaa M. Abu-Melha ◽  
Diaa A. Ibrahim
Keyword(s):  
Colon Cancer ◽  
Molecular Docking ◽  
Anticancer Agents ◽  
Tyrosine Kinases ◽  
Hct116 Cell ◽  
Human Colon ◽  
Docking Studies ◽  
Coumarin Derivatives ◽  
Human Colon Cancer

A series of novel coumarin derivatives carrying 1,2,4-triazole or 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole moieties were prepared and evaluated in vitro as anticancer in the human colon cancer (HCT116) cell line. The derivatives 4c and 8c exhibited marked anticancer activity with IC50 values 4.363 and 2.656 µM, respectively. The molecular docking studies suggested possible interaction with tyrosine kinases (CDK2).

scholarly journals Tel-Cu-NPs Catalyst: Synthesis of Naphtho[2,3-g]phthalazine Derivatives as Potential Inhibiters of Tyrosinase Enzymes and Their Investigation in Kinetic, Molecular Docking, and Cytotoxicity Studies

Catalysts ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1442
Author(s):  
Keerthana Selvaraj ◽  
Ali Daoud ◽  
Saud Alarifi ◽  
Akbar Idhayadhulla
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Kojic Acid ◽  
Docking Studies ◽  
Kinetic Behavior ◽  
One Pot ◽  
Catalyst Synthesis ◽  
Cytotoxicity Activity ◽  
Cytotoxicity Studies ◽  
High Yields

Novel one-pot synthesis naphtho[2,3-g]phthalazine (1a–1k) of Mannich base derivatives can be achieved via grindstone chemistry using a Tel-Cu-NPs (telmisartan-copper nanoparticles) catalyst. This method offers efficient mild reaction conditions and high yields. Tyrosinase inhibitory activity was evaluated for all synthesized compounds, along with analysis of kinetic behavior and molecular docking studies. The synthesized compound, 1c was (IC50 = 11.5 µM) more active than kojic acid (IC50 = 78.0 µM). Lineweaver Burk plots were used to analyze the kinetic behavior of the most active compound 1c, it was reversible and competitive behavior. Compound 1c and kojic acid occurred in the presence of 2-hydroxyketone, which has the same inhibitory mechanism. The molecular docking of compound 1c and the control kojic acid were docked against 2Y9X protein via the Schrodinger Suite. The compound 1c showed a respectable dock score (−5.6 kcal/mol) compared to kojic acid with a dock score of (−5.2 kcal/mol) in the 2Y9X protein. Cytotoxicity activity was also evaluated by using HepG2 (liver), MCF-7 (breast), and HeLa (cervical) cancer cell lines, and high activity for 1c (GI50 = 0.01, 0.03, and 0.04 µM, respectively) against all cell lines was found compared to standard and other compounds. Therefore, this study succeeded in testing a few promising molecules as potential antityrosinase agents.

scholarly journals Synthesis, Antiproliferative Activity and Molecular Docking Studies of Novel Doubly Modified Colchicine Amides and Sulfonamides as Anticancer Agents

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1789 ◽  
Author(s):  
Julia Krzywik ◽  
Witold Mozga ◽  
Maral Aminpour ◽  
Jan Janczak ◽  
Ewa Maj ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Docking Studies ◽  
Binding Modes ◽  
Colchicine Binding Site ◽  
3T3 Cell Lines ◽  
Colchicine Derivatives

Colchicine is a well-known compound with strong antiproliferative activity that has had limited use in chemotherapy because of its toxicity. In order to create more potent anticancer agents, a series of novel colchicine derivatives have been obtained by simultaneous modification at C7 (amides and sulfonamides) and at C10 (methylamino group) positions and characterized by spectroscopic methods. All the synthesized compounds have been tested in vitro to evaluate their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX and BALB/3T3 cell lines. Additionally, the activity of the studied compounds was investigated using computational methods involving molecular docking of the colchicine derivatives to β-tubulin. The majority of the obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin or cisplatin against tested cancer cell lines. Furthermore, molecular modeling studies of the obtained compounds revealed their possible binding modes into the colchicine binding site of tubulin.

scholarly journals Synthesis, Antiproliferative Activity and Molecular Docking Studies of 1,3,5-Triaryl Pyrazole Compound as Estrogen α Receptor Inhibitor Targeting MCF-7 Cells Line

Molekul ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 18
Author(s):  
Noval Herfindo ◽  
Riska Prasetiawati ◽  
Daniel Sialagan ◽  
Neni Frimayanti ◽  
Adel Zamri
Keyword(s):  
Molecular Docking ◽  
Antiproliferative Activity ◽  
Docking Simulation ◽  
Docking Studies ◽  
Biological Evaluation ◽  
One Pot ◽  
Vitro Assay ◽  
Oxidative Aromatization ◽  
Mcf 7

This research has been successfully synthesized three compounds of 1,3,5-triaryl pyrazole derivatives by two steps reaction. Firstly, pyrazoline (4a-c) compound was obtained by one-pot reaction of aromatic ketones, aldehyde and hydrazine in basic condition. Then, pyrazole (5a-c) compound was obtained by oxidative aromatization of compound 4 in the presense of acetic acid. Chemical structure of predicted molecules was confirmed by FTIR, NMR and HRMS spectroscopy data analysis. Antiproliferative activity of compound 5a-c were evaluated by in vitro assay against MCF-7 cells line and molecular docking simulation against ERα (PDB ID: 3ERT) using MOE 2019. Biological evaluation result showed that pyrazole compounds had weak antiproliferative activity against MCF-7 cells with IC50 were > 1000 µM, whereas the docking studies agrees the result.

scholarly journals Microwave Assisted One-Pot Three-Component Synthesis of Novel Pyranocarbazole Derivatives as Antiproliferative Agents and Molecular Docking Studies

2019 ◽  
Vol 31 (4) ◽  
pp. 785-792
Author(s):  
Bobbala Ramana Reddy ◽  
Pedavenkatagari Narayana Reddy
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Knoevenagel Condensation ◽  
Docking Studies ◽  
Atom Economy ◽  
Chromatographic Purification ◽  
One Pot ◽  
Molecular Docking Studies ◽  
Lead Compounds ◽  
Colchicine Binding Site

A new series of pyrano[3,2-c]carbazole and pyrano[2,3-a]carbazole derivatives have been synthesized by one-pot three-component coupling of 4-hydroxycarbazole or 2-hydroxycarbazole, aromatic substituted aldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine under microwave irradiation. This transformation presumably occurs via Knoevenagel condensation-Michael addition–tautomerism intramolecular O-cyclization-elimination sequence of reactions creating one C-O bond and two C-C bonds. The significant features of this one-pot reaction include catalyst free, solvent free, atom-economy, no column chromatographic purification, short reaction time and good yield. Further, the synthesized pyranocarbazole derivatives were evaluated for their antiproliferative activity against four cancer cell lines such as DU 145 (prostate cancer), MDA-MB-231 (breast cancer), SKOV3 (ovarian cancer) and B16-F10 (skin cancer). The results clearly demonstrated that trimethoxyphenyl substituted pyrano[3,2-c]carbazole (9h) exhibited most potent antriproliferative activity against tested cell lines. Compounds 9a, 9b and 11a were also displayed pronounced antriproliferative activity. In addition, molecular docking studies revealed that the lead compounds bind to the colchicine binding site of the tubulin effectively.

Hybrids of Quinoline and Anilinopyrimidine: Novel EGFRT790M Inhibitors with Antiproliferative Activity against Non-Small Cell Lung Cancer Cell Lines

2020 ◽  
Vol 20 (6) ◽  
pp. 724-733
Author(s):  
Chun Han ◽  
Jiahong Ren ◽  
Feng Su ◽  
Xiaoqin Hu ◽  
Mengyao Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Antiproliferative Activity ◽  
Docking Studies ◽  
Small Cell ◽  
Small Cell Lung ◽  
Molecular Docking Studies

Background: The third-generation irreversible Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) inhibit the T790M mutation while sparing EGFRWT. However, the C797S point mutation confers resistance to existing irreversible EGFRT790M inhibitors. Objective: Novel EGFRT790M inhibitors were designed through hybridization of quinoline and anilinopyrimidine, and biologically evaluated their antiproliferative activity against Non-Small Cell Lung Cancer (NSCLC) cell lines. Methods: The target compounds 11a-h were synthesized and structurally characterized with 1H, 13C Nuclear Magnetic Resonance (NMR) spectroscopy and High-Resolution Mass Spectrometry (HRMS). Their inhibitory effects on tumor cell proliferation and EGFR kinase were biologically evaluated. Additionally, molecular docking studies were also performed on the representative typical EGFRT790M inhibitor. Results: Most of the evaluated compounds displayed moderate antiproliferative activity on H1975 cells with EGFRL858R/T790M. However, compound 11a (IC50 = 2.235 ± 0.565μM) showed stronger inhibition than gefitinib (IC50 = 8.830 ± 0.495μM) in concentration- and time-dependent manner. Moreover, compound 11a exhibited weaker inhibitory activities on cells with EGFRWT. Specifically, compound 11a strongly suppressed EGFRL858R/T790M (IC50 = 0.515 ± 0.011μM) relative to EGFRWT (IC50 = 0.913 ± 0.068μM). Furthermore, molecular docking studies demonstrated its strong binding contacts with the EGFRT790M enzyme through hydrogen bonds and other non-bonded interactions. Conclusion: Taken together, these results indicate that the hybrid of quinoline and anilinopyrimidine 11a, could be a potential inhibitor of EGFRT790M in NSCLC, which warrants further in-depth studies.

Arylhydrazono/Aryldiazenyl Pyrazoles: Green One-Pot Solvent-Free Synthesis and Anticancer Evaluation

2020 ◽  
Vol 17 (10) ◽  
pp. 772-778
Author(s):  
Abdulrhman Alsayari ◽  
Abdullatif Bin Muhsinah ◽  
Yahya I. Asiri ◽  
Jaber Abdullah Alshehri ◽  
Yahia N. Mabkhot ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Binding Mode ◽  
Docking Studies ◽  
Solvent Free ◽  
Pyrazole Derivatives ◽  
One Pot ◽  
Solvent Free Conditions ◽  
Hybrid Molecules

The aim of this study was to synthesize and evaluate the biological activity of pyrazole derivatives, in particular, to perform a “greener” one-pot synthesis using a solvent-free method as an alternative strategy for synthesizing hydrazono/diazenyl-pyridine-pyrazole hybrid molecules with potential anticancer activity. Effective treatment for all types of cancers is still a long way in the future due to the severe adverse drug reactions and drug resistance associated with current drugs. Therefore, there is a pressing need to develop safer and more effective anticancer agents. In this context, some hybrid analogues containing the bioactive pharmacophores viz. pyrazole, pyridine, and diazo scaffolds were synthesized by one-pot method. Herein, we describe the expedient synthesis of pyrazoles by a onepot three-component condensation of ethyl acetoacetate/acetylacetone, isoniazid, and arenediazonium salts under solvent-free conditions, and the evaluation of their cytotoxicity using a sulforhodamine B assay on three cancer cell lines. Molecular docking studies employing tyrosine kinase were also carried out to evaluate the binding mode of the pyrazole derivatives under study. 1-(4-Pyridinylcarbonyl)-3- methyl-4-(2-arylhydrazono)-2-pyrazolin-5-ones and [4-(2-aryldiazenyl)-3,5-dimethyl-1H-pyrazol-1- yl]-4-pyridinylmethanones, previously described, were prepared using an improved procedure. Among these ten products, 1-isonicotinoyl-3-methyl-4-[2-(4-nitrophenyl)hydrazono]-2-pyrazolin-5-one (1f) displayed promising anticancer activity against the MCF-7, HepG2 and HCT-116 cell lines, with an IC50 value in the range of 0.2-3.4 μM. In summary, our findings suggest that pyrazoles containing hydrazono/ diazenyl and pyridine pharmacophores constitute promising scaffolds for the development of new anticancer agents.

Sign in / Sign up

Export Citation Format

Share Document