Pot-economic synthesis of diarylpyrazoles and pyrimidines involving Pd-catalyzed cross-coupling of 3-trifloxychromone and triarylbismuth

Kumar, Abhijeet; Rao, Maddali L. N.

doi:10.1007/s12039-018-1565-6

Cited by 13 publications

(9 citation statements)

References 42 publications

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“…The 3,4-diarylpyrazoles was synthesized as described in detail earlier [ 4 ], following the reaction sequence presented in Figure 2 [ 4 ]. In detail, 3-trifloxychromone and triarylbismuths were used for the one-pot synthesis of 3,4-diarylpyrazoles as per described protocol [ 11 , 12 , 13 ].…”

Section: Methodsmentioning

confidence: 99%

“…In general, the naturally occurring heterocyclic compounds along with their synthetic analogues are found to display a vast variety of biological activities [ 1 , 2 , 3 , 4 ]. N -heterocycles such as functionalized pyroles, pyrimidines, pyridine, pyrazoles etc.…”

Section: Introductionmentioning

confidence: 99%

“…Celecoxib and Ruxolitinib are anti-inflammatory and anti-cancerous drugs respectively containing pyrazole scaffolds [ 7 , 8 ]. Apart from these examples, various other pyrazole based drugs are known in the literature and available in the market also [ 4 ]. In addition to that several research groups are involved in the synthesis of new pyrazole derivatives and exploration of their biological activities.…”

Section: Introductionmentioning

confidence: 99%

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Novel 3,4-diarylpyrazole as prospective anti-cancerous agents

Pandey

Tripathi

Kumar

et al. 2020

Heliyon

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Cancer is a leading cause of death globally. Despite therapeutic advancements the mortality rate of cancer is continuously increasing. Thus, it is important to identify and design potential therapeutic agents which can specifically bind with most common targets of cancer and inhibit tumor progression. The present work discloses the potential therapeutic application of the novel 3,4-diaryl 1 H -pyrazoles as prospective anti-cancerous agent. The in silico molecular docking studies performed with 3,4-disubstituted pyrazoles as ligand with targets including DNA, BCL-2 and F1-ATP Synthase revealed strong binding affinity with DNA (-7.5 kcal/mol), BCL-2 (-8.1 kcal/mol) and F1-ATP Synthase (-7.2 kcal/mol). Furthermore, the in silico finding was validated with the in vitro cytotoxicity assay with human breast cancer cell line (MDA-MB-231). MDA-MB-231 cells treated with 3,4-diarylpyrazole resulted in an increase in annexin-V positive cells, production of reactive oxygen species (ROS), dissipation of the mitochondrial membrane potential and activation of caspase-3. Taken together, this study demonstrate that a novel synthesized 3,4-diarylpyrazoles, showed strong binding affinity against DNA, anti-proliferative activity and executed apoptosis through ROS-dependent caspase-3-mediated mitochondrial intrinsic apoptotic pathway against MDA-MB-231 cells. These findings increase our understanding of the molecular mechanism (s) by which 3,4-diarylpyrazoles can exert their anticancer activity and may contribute towards development of novel therapeutic agent against breast cancer.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel 3,4-diarylpyrazole as prospective anti-cancerous agents

Pandey

Tripathi

Kumar

et al. 2020

Heliyon

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“…For example, Dayvigo (Lemborexant), Inrebic (Fedratinib) are a few examples of drugs containing pyrimidine scaffolds which received FDA-approval in 2019. Because of the enormous therapeutic importance, we selected some well-characterized pyrimidine substituted phenols (Kumar & Rao, 2018; Table S1, supplementary material) to investigate their efficiency in binding to the interface of the hACE2-S protein complex and modulate the pattern of infectivity of the SARS-CoV-2 virus. In this study, we aim to identify diaryl pyrimidine derivatives as a potential lead molecule which may bind at the interface of the hACE2-S protein complex with high affinity.…”

Section: Introductionmentioning

confidence: 99%

Targeting virus–host interaction by novel pyrimidine derivative: anin silicoapproach towards discovery of potential drug against COVID-19

Rane

Pandey

Chatterjee

et al. 2020

Journal of Biomolecular Structure and Dynamics

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The entire human population over the globe is currently facing appalling conditions due to the spread of infection from coronavirus disease-2019 (COVID-19). The spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present on the surface of the virion mediates the virus entry into the host cells and therefore is targeted by several scientific groups as a novel drug target site. The spike glycoprotein binds to the human angiotensin-converting enzyme-2 (hACE2) cell surface receptor abundantly expressed in lung tissues, and this binding phenomenon is a primary determinant of cell tropism and pathogenesis. The binding and internalization of the virus is the primary and most crucial step in the process of infection, and therefore the molecules targeting the inhibition of this process certainly hold a significant therapeutic value. Thus, we systematically applied the computational techniques to identify the plausible inhibitor from a chosen set of well characterized diaryl pyrimidine analogues which may disrupt interfacial interaction of spike glycoprotein (S) at the surface of hACE2. Using molecular docking, molecular dynamics (MD) simulation and binding free energy calculation, we have identified AP-NP (2-(2-amino-5-(naphthalen-2-yl)pyrimidin-4-yl)phenol), AP-3-OMe-Ph (2-(2-amino-5-(3-methoxyphenyl)pyrimidin-4-yl)phenol) and AP-4-Me-Ph (2-(2-amino-5-(p-tolyl) pyrimidin-4-yl)phenol) from a group of diaryl pyrimidine derivatives which appears to bind at the interface of the hACE2-S complex with low binding free energy. Thus, pyrimidine derivative AP-NP may be explored as an effective inhibitor for hACE2-S complex. Furthermore, in vitro and in vivo studies will strengthen the use of these inhibitors as suitable drug candidates against SARS-COV-2. Abbreviations: 6-HB: six-helix bundle; ADME: absorption, distribution, metabolism and excretion; AP-NP: 2-(2-amino-5-(naphthalen-2-yl)pyrimidin-4-yl) phenol; AP-4-Me-Ph: 2-(2-amino-5-(p-tolyl)pyrimidin-4yl) phenol; AP-3-OMe-Ph: 2-(2-amino-5-(3-methoxyphenyl)pyrimidin-4-yl) phenol; COVID-19: coronavirus disease 2019; CQ: chloroquine; hACE2: human angiotensin converting enzyme-2; hACE2-S protein complex: human angiotensin converting enzyme-2 receptor and severe acute respiratory syndrome coronavirus 2 spike protein complex; HR1: heptad repeat 1; HR2: heptad repeat 2; PDB: protein data bank; RBD: receptor-binding domain; SARS-CoV-2S: severe acute respiratory syndrome coronavirus 2 spike protein; TMPRSS-2: transmembrane protease serine 2

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“…For example, Dayvigo (Lemborexant), Inrebic (Fedratinib) are few examples of drugs containing pyrimidine scaffolds which received FDA-approval in 2019. Because of the enormous therapeutic importance, we selected some well characterized pyrimidine substituted phenols (Kumar & Rao 2018) (Table S1) to investigate their inhibitory action against SARS-CoV-2 virus through molecular docking.…”

Section: Introductionmentioning

confidence: 99%

Targeting Virus-Host Interaction: An in Silico Approach to Develop Promising Inhibitors Against COVID-19

Subhash¹,

Rane²,

Aroni³

et al. 2020

Preprint

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The entire human population all over the globe is currently facing appalling conditions due to the spread of infection from COVID-19 (corona virus disease-2019). In the last few months enormous amount of studies have been continuously trying to target several potential drug sites to identify a novel therapeutic target. Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also being targeted by several scientific groups as a novel drug target. The spike glycoprotein protein is present on the surface of the virion and binds to the human angiotensin-converting enzyme-2 (hACE2) membrane receptor thereby promoting its fusion to the host cell membrane. The binding and internalization of the virus is a crucial step in the process of infection and hence any molecule that can inhibit this, certainly holds a significant therapeutic value. We have identified AP-NP (2-(2-amino-5-(naphthalen-2- yl)pyrimidin-4-yl)phenol) and AP-4-Me-Ph (2-(2-amino-5-(p-tolyl)pyrimidin-4-yl)phenol) from a group of diaryl pyrimidine derivatives which appear to bind at the interface of hACE2-SARS-CoV-2S complex (human angiotensin converting enzyme 2 and spike glycoprotein complex) with a low binding energy (<-8 Kcal/mol). In this in-silico study we also found that AP-NP interacts with S1 domain of C-terminal part of SARS-CoV-2S however AP-4-Me-Ph was found to interact with S2 domain of SARS-CoV-2S. The result suggested that AP-NP and AP-4-Me-Ph have potential to inhibit the interaction between spike protein and hACE2 receptor also AP-4-Me-Ph might be prevent internalization of the virion within the host. Further in vitro and in vivo study will strengthen these drug candidates against the COVID-19.

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Pot-economic synthesis of diarylpyrazoles and pyrimidines involving Pd-catalyzed cross-coupling of 3-trifloxychromone and triarylbismuth

Cited by 13 publications

References 42 publications

Novel 3,4-diarylpyrazole as prospective anti-cancerous agents

Novel 3,4-diarylpyrazole as prospective anti-cancerous agents

Targeting virus–host interaction by novel pyrimidine derivative: anin silicoapproach towards discovery of potential drug against COVID-19

Targeting Virus-Host Interaction: An in Silico Approach to Develop Promising Inhibitors Against COVID-19

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