Target fishing and docking studies of the novel derivatives of aryl-aminopyridines with potential anticancer activity

Background & Objective:New diaryl-substituted pyrimidinedione compounds, their thioxo derivatives as well as their bicyclic thiazole compounds were synthesized and characterized.Methods:The glycosylamino derivatives of the synthesized disubstituted derivatives of the pyrimidine scaffold were also prepared via reaction of the N3-amino derivatives with a number of monosaccharides followed by acetylation.Results:The anticancer activity of the synthesized compounds was studied against human liver cancer (HepG2) and RPE-1cell lines. Compounds 2a, 2b, 3a and 12 showed potent activities with IC50 results comparable to that of doxorubicin.Conclusion:Docking investigations into Cyclin-dependent kinase 2 (CDK-2) enzyme, a potential target for cancer medication, were also reported showing the possible binding interaction into the enzyme active site to support their activity behavior.

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SYNTHESIS, ANTICANCER ACTIVITY AND MOLECULAR DOCKING STUDIES OF SOME NOVEL QUINOLINE HYDRAZIDE DERIVATIVES OF SUBSTITUTED BENZALDEHYDES

RASAYAN Journal of Chemistry ◽

10.31788/rjc.2019.1225137 ◽

2019 ◽

Vol 12 (02) ◽

pp. 880-890

Author(s):

Venkatareddy Gayam ◽

Subban Ravi ◽

G.M.V .N.A.R. Ravikumar ◽

Arumugam Thangamani

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Docking Studies ◽

Molecular Docking Studies ◽

Substituted Benzaldehydes ◽

Derivatives Of

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

Letters in Organic Chemistry ◽

10.2174/1570178617666200320104923 ◽

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.

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

Current Bioactive Compounds ◽

10.2174/1573407213666170828165512 ◽

2019 ◽

Vol 15 (2) ◽

pp. 257-267 ◽

Cited By ~ 3

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.

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Structural and Molecular Docking Studies of 4-Benzyl-3-[(1-methylpyrrol- 2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one with Anticancer Activity

Medicinal Chemistry ◽

10.2174/1573406411309030002 ◽

2013 ◽

Vol 9 (3) ◽

pp. 313-328 ◽

Cited By ~ 5

Author(s):

Agnieszka A. Kaczor ◽

Monika Pitucha ◽

Zbigniew Karczmarzyk ◽

Waldemar Wysocki ◽

Jolanta Rzymowska ◽

...

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Docking Studies ◽

Molecular Docking Studies

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Design, Synthesis and Biological Evaluation of Novel Urea and Thiourea Bearing thieno[3,2-d]-pyrimidines as PI3 Kinase Inhibitors

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180209151018 ◽

2018 ◽

Vol 18 (6) ◽

pp. 891-902 ◽

Cited By ~ 6

Author(s):

Srinu Bodige ◽

Parameshwar Ravula ◽

Kali Charan Gulipalli ◽

Srinivas Endoori ◽

J.N. Narendra Sharath Chandra ◽

...

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Inhibitory Activity ◽

Intracellular Signaling ◽

Research Work ◽

Docking Studies ◽

Biological Evaluation ◽

Intracellular Enzyme ◽

Ht 29 ◽

Mcf 7

Background: Phosphatidylinositol-3-kinase α (PI3Kα) is a ubiquitous intracellular enzyme, mainly involved in intracellular signaling pathways, promotes cellular growth, proliferation, and differentiation. Therefore, inhibition of PI3K can be a hotspot in molecular targeted therapy for the treatment of cancer. Methods: The present research work involves molecular docking studies performed to screen derivatives of urea and thiourea bearing thieno [3,2-d]-pyrimidines against the active site of PI3K enzyme using MOE.2008.10. The designed structures (6a-f) and (7a-j) were synthesized by the facile synthetic methods and evaluated for their anticancer activity against HT-29 and MCF-7 cell lines and inhibitory activity against PI3Kα enzyme. Results: Among the tested compounds, 4-(4-(2-(3-(pyrimidin-2-yl)thioureido)ethyl)piperazin-1-yl)thieno[3,2- d]pyrimidine-6-carboxamide (7f) showed the highest anticancer activity against HT-29 and MCF-7 cell lines with IC50 values of 2.18 µM and 4.25 µM, respectively. Further, the same compound also exhibited potent PI3Kα inhibitory activity with IC50 value of 1.26 µM. Conclusion: Docking studies supported the initial pharmacophoric hypothesis and suggested a mode of interaction at the active binding site of PI3Kα, demonstrating that the target compounds were potential inhibitory agents for cancer therapy.

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Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors

Zeitschrift für Naturforschung C ◽

10.1515/znc-2020-0104 ◽

2020 ◽

Vol 75 (9-10) ◽

pp. 353-362

Author(s):

Begüm Nurpelin Sağlık ◽

Ahmet Mücahit Şen ◽

Asaf Evrim Evren ◽

Ulviye Acar Çevik ◽

Derya Osmaniye ◽

...

Keyword(s):

Anticancer Activity ◽

In Silico ◽

Biological Effects ◽

Docking Studies ◽

Benzimidazole Derivatives ◽

Binding Modes ◽

Reference Drug ◽

In Silico Studies ◽

New Compounds ◽

Mcf 7

AbstractInhibition of aromatase enzymes is very important in the prevention of estrogen-related diseases and the regulation of estrogen levels. Aromatase enzyme is involved in the final stage of the biosynthesis of estrogen, in the conversion of androgens to estrogen. The development of new compounds for the inhibition of aromatase enzymes is an important area for medicinal chemists in this respect. In the present study, new benzimidazole derivatives have been designed and synthesized which have reported anticancer activity in the literature. Their anticancer activity was evaluated against human A549 and MCF-7 cell lines by MTT assay. In the series, concerning MCF-7 cell line, the most potent compounds were the 4-benzylpiperidine derivatives 2c, 2g, and 2k with IC50 values of 0.032 ± 0.001, 0.024 ± 0.001, and 0.035 ± 0.001 µM, respectively, compared to the reference drug cisplatin (IC50 = 0.021 ± 0.001 µM). Then, these compounds were subject to further in silico aromatase enzyme inhibition assays to determine the possible binding modes and interactions underlying their activity. Thanks to molecular docking studies, the effectiveness of these compounds against aromatase enzyme could be simulated. Consequently, it has been found that these compounds can be settled very properly to the active site of the aromatase enzyme.

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Biguanide-Based Synthesis of 1,3,5-Triazine Derivatives with Anticancer Activity and 1,3,5-Triazine Incorporated Calcium Citrate Nanoparticles

Molecules ◽

10.3390/molecules26041028 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1028

Author(s):

Monnaya Chalermnon ◽

Sarocha Cherdchom ◽

Amornpun Sereemaspun ◽

Rojrit Rojanathanes ◽

Tanatorn Khotavivattana

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Anticancer Agent ◽

Drug Loading ◽

Calcium Citrate ◽

Colorectal Cancer Cell Lines ◽

Triazine Derivatives ◽

Further Development ◽

Derivatives Of ◽

Potential Use

Twelve derivatives of biguanide-derived 1,3,5-triazines, a promising class of anticancer agent, were synthesised and evaluated for their anticancer activity against two colorectal cancer cell lines—HCT116 and SW620. 2c and 3c which are the derivatives containing o-hydroxyphenyl substituents exhibited the highest activity with IC50 against both cell lines in the range of 20–27 µM, which is comparable to the IC50 of cisplatin reference. Moreover, the potential use of the calcium citrate nanoparticles (CaCit NPs) as a platform for drug delivery system was studied on a selected 1,3,5-triazine derivative 2a. Condition optimisation revealed that the source of citrate ions and reaction time significantly influence the morphology, size and %drug loading of the particles. With the optimised conditions, “CaCit-2a NPs” were successfully synthesised with the size of 148 ± 23 nm and %drug loading of up to 16.3%. Furthermore, it was found that the release of 2a from the synthesised CaCit-2a NPs is pH-responsive, and 2a could be control released under the acidic cancer environment. The knowledge from this study is perceptive for further development of the 1,3,5-triazine-based anticancer drugs and provide the platform for the incorporation of other drugs in the CaCit NPs in the future.

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Tumor Necrosis Factor-α Production-Enhancing Properties of Novel Adamantylalkylthio Derivatives of Some Heterocyclic Compounds

Zeitschrift für Naturforschung B ◽

10.1515/znb-2005-0419 ◽

2005 ◽

Vol 60 (4) ◽

pp. 471-475 ◽

Cited By ~ 2

Author(s):

Barbara Orzeszko ◽

Tomasz Świtaj ◽

Anna B. Jakubowska-Mućka ◽

Witold Lasek ◽

Andrzej Orzeszko ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Heterocyclic Compounds ◽

Tumor Necrosis ◽

The Novel ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Factor Α ◽

Derivatives Of ◽

Necrosis Factor

Certain adamantylated heterocycles were previously shown to enhance the secretion of tumor necrosis factor alpha (TNF-α) by murine melanoma cells that have been transduced with the gene for human TNF-α and constitutively expressed this cytokine. The stimulatory potency of those compounds depended, among other factors, on the structure of the linker between the adamantyl residue and the heterocyclic core. In the present study, a series of (1-adamantyl)alkylsulfanyl derivatives of heterocyclic compounds was prepared by alkylation of the corresponding thioheterocyles. Of the novel adamantylalkylthio compounds tested in the aforementioned cell line, 2-(2-adamantan-1-ylethylsulfanyl)- 4-methyl-pyrimidine was found to be the most active

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