Synthesis and docking studies of some novel quinoline derivatives bearing a sulfonamide moiety as possible anticancer agents

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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Insilico studies, synthesis and antitubercular activity of some novel quinoline – azitidinone derivatives

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200129095952 ◽

2020 ◽

Vol 16 ◽

Author(s):

Trupti. S. Chitre ◽

Kalyani. D. Asgaonkar ◽

Amrut B. Vikhe ◽

Shital M Patil ◽

Dinesh. R. Garud ◽

...

Keyword(s):

Combinatorial Library ◽

3D Qsar ◽

Antitubercular Activity ◽

Structural Features ◽

Docking Studies ◽

Quinoline Derivatives ◽

Qsar Models ◽

Molecular Modeling Studies ◽

Lead Generation ◽

Mcf 7

Background: Diarylquinolines like Bedaquiline have shown promising antitubercular activity by their action of Mycobacterial ATPase. Objective: The structural features necessary for good antitubercular activity for a series of quinoline derivatives were explored through computational chemistry tools like QSAR and combinatorial library generation. In the current study, 3-Chloro-4-(2-mercaptoquinoline-3-yl)-1-substitutedphenylazitidin-2-one derivatives have been designed and synthesized based on molecular modeling studies as anti-tubercular agents. Method: 2D and 3DQSAR analysis was used to designed compounds having quinoline scaffold. The synthesized compounds were evaluated against active and dormant strains of Mycobacterium tuberculosis (MTB) H37 Ra and Mycobacterium bovis BCG. The compounds were also tested for cytotoxicity against MCF-7, A549 and Panc-1 cell lines using MTT assay. Binding affinity of designed compounds was gauged by molecular docking studies. Results: Statistically significant QSAR models generated by SA-MLR method for 2D QSAR exhibited r2 = 0.852, q2 = 0.811and whereas 3D QSAR with SA-kNN showed q2 = 0.77. The synthesized compounds exhibited MIC in the range of 1.38-14.59(µg/ml) .These compounds showed some crucial interaction with MTB Atpase. Conclusion: The present study has shown some promising results which can be further explored for lead generation.

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Recent Development of Sulfonyl or Sulfonamide Hybrids as Potential Anticancer Agents: A Key Review

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666171103140749 ◽

2018 ◽

Vol 18 (4) ◽

pp. 488-505 ◽

Cited By ~ 32

Author(s):

K. P. Rakesh ◽

Shi-Meng Wang ◽

Jing Leng ◽

L. Ravindar ◽

Abdullah M. Asiri ◽

...

Keyword(s):

Drug Resistance ◽

Anticancer Agents ◽

Side Effect ◽

Docking Studies ◽

Multi Drug Resistance ◽

Anticancer Activities ◽

Pharmacological Activities ◽

Synthetic Compounds ◽

Structure Activity ◽

Anticancer Drug Discovery

Cancer is the second leading cause of death worldwide. There is always a huge demand for novel anticancer drugs and diverse new natural or synthetic compounds are developed continuously by scientists. Presently, a large number of drugs in clinical practice have showed pervasive side effect and multidrug resistance. Sulfonyl or sulfonamide hybrids became one of the most attractive subjects due to their broad spectrum of pharmacological activities. Sulfonyl hybrids were broadly explored for their anticancer activities and it was found that they possess minimum side effect along with multi-drug resistance activity. This review describes the most recent applications of sulfonyl hybrid analogues in anticancer drug discovery and further discusses the mechanistic insights, structure-activity relationships and molecular docking studies for the potent derivatives.

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Synthesis, biological evaluation and molecular docking studies of 1,3-benzoxazine derivatives as potential anticancer agents

Medicinal Chemistry Research ◽

10.1007/s00044-013-0534-3 ◽

2013 ◽

Vol 22 (11) ◽

pp. 5256-5266 ◽

Cited By ~ 8

Author(s):

Vikas Garg ◽

Ankit Kumar ◽

Anurag Chaudhary ◽

Saurabh Agrawal ◽

Praveen Tomar ◽

...

Keyword(s):

Molecular Docking ◽

Anticancer Agents ◽

Docking Studies ◽

Biological Evaluation ◽

Molecular Docking Studies

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Design, synthesis, cytotoxicity, HuTopoIIα inhibitory activity and molecular docking studies of pyrazole derivatives as potential anticancer agents

Bioorganic Chemistry ◽

10.1016/j.bioorg.2016.10.001 ◽

2016 ◽

Vol 69 ◽

pp. 77-90 ◽

Cited By ~ 21

Author(s):

Raquib Alam ◽

Divya Wahi ◽

Raja Singh ◽

Devapriya Sinha ◽

Vibha Tandon ◽

...

Keyword(s):

Molecular Docking ◽

Anticancer Agents ◽

Inhibitory Activity ◽

Docking Studies ◽

Pyrazole Derivatives ◽

Design Synthesis ◽

Molecular Docking Studies

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6,7-Disubstituted-4-anilinoquinazoline: Design, Synthesis and Anticancer Activity as a Novel Series of Potent Anticancer Agents

Pharmaceutical Sciences ◽

10.34172/ps.2020.72 ◽

2020 ◽

Vol 27 (2) ◽

pp. 209-218

Author(s):

Fatemeh Azmian Moghadam ◽

Mehdi Evazalipour ◽

Hassan Kefayati ◽

Saeed Ghasemi

Keyword(s):

Growth Factor ◽

Anticancer Agents ◽

Growth Factor Receptor ◽

Docking Studies ◽

Anticancer Activities ◽

Design Synthesis ◽

Atp Binding Site ◽

Novel Approach ◽

Epidermal Growth ◽

Endothelial Growth Factor

Background: Epidermal Growth Factor Receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are responsible for several pathological conditions such as the development of different kinds of tumors. The combined inhibition of both signal transduction pathways seems to be a promising novel approach for cancer treatment. Methods: In this study, novel 4-anilinoquinazoline derivatives with various substituents on-7 position of quinazoline moiety were designed, synthesized, and evaluated for their antiproliferative activity against A431 and HU02 cell lines. Results: Compounds 8a, 8d, and 8f displayed the most potent anticancer activities against A431(IC50 = 1.78 μM, 8.25 μM, and 7.18 μM, respectively) in comparison with reference standards(erlotinib IC50=8.31 μM and vandetanib IC50=10.62 μM). Molecular docking studies proved that8a as the most potent compound could be efficiently accommodated in the ATP binding site ofEGFR and VEGFR-2 through the formation of essential hydrogen bonds between quinazolineN1 atom and the Met796 backbone of EGFR as well as the Cys919 backbone of VEGFR-2 with a distance of 1.94 Å and 1.398 Å, respectively. Conclusion: Compound 8a as the most potent compound with morpholine and 3-bromoaniline at the 7 and 4 positions of quinazoline scaffold, respectively, deserves more study and structural optimization as an anticancer agent.

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