Identification of potential Aurora kinase-C protein inhibitors: an amalgamation of energy minimization, virtual screening, prime MMGBSA and AutoDock

Bathula, Revanth; Lanka, Goverdhan; Muddagoni, Narasimha; Dasari, Mahendar; Nakkala, Sravanthi; Bhargavi, Manan; Somadi, Gururaj; Sivan, Sree Kanth; Potlapally, Sarita Rajender

doi:10.1080/07391102.2019.1630318

Cited by 16 publications

(10 citation statements)

References 54 publications

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“…The cognate molecule VX‐680 binds at the cavity formed by hydrophobic amino acids, Leu49, Lys51, Lys53, Phe54, Ala70, Leu104, Leu120, Tyr122, Ala123, Glu127, and Asp184 22 . Residues Ala123 and Glu127 present at the hinge region were hydrogen‐bonded with VX‐680 while Phe54 formed π–π interaction with its benzene ring (Figure S3C).…”

Section: Resultsmentioning

confidence: 99%

“…The cognate molecule VX-680 binds at the cavity formed by hydrophobic amino acids, Leu49, Lys51, Lys53, Phe54, Ala70, Leu104, Leu120, Tyr122, Ala123, Glu127, and Asp184. 22 Residues Ala123 and Glu127 present at the hinge region were hydrogen-bonded with VX-680 while Phe54 formed π-π interaction with its benzene ring (Figure S3C). Further, in AURK-C, the hydroxyl phenyl and triazole moiety of molecule 2818, form hydrogen-bonding interactions with Lys51 and Ala123 residues of the catalytic site (Figure 2I).…”

Section: Structure-based Virtual Screening and Molecular Dockingmentioning

confidence: 99%

“…Overexpression of AURK‐C has been reported in the thyroid, placenta, and meiotically dividing gametes 12 . The aberrant expression of AURK‐C increases the depletion of AURK‐B in SAC 22 . This leads to impairment of SAC and ultimately chromosome instability and promotion of various cancers.…”

Section: Introductionmentioning

confidence: 99%

“…12 The aberrant expression of AURK-C increases the depletion of AURK-B in SAC. 22 This leads to impairment of SAC and ultimately chromosome instability and promotion of various cancers. AURKs are, thus, involved in a wide range of cancers and hence, lent an interest as potential drug targets for the development of new anticancer therapies.…”

Section: Introductionmentioning

confidence: 99%

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Identification of polypharmacological anticancerous molecules against Aurora kinase family of proteins

Gupta

Kumar

Singh

et al. 2022

J of Cellular Biochemistry

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The Human Aurora Kinase (AURK) protein family is the key player of cell cycle events including spindle assembly, kinetochore formation, chromosomal segregation, centrosome separation, microtubule dynamics, and cytokinesis. Their aberrant expression has been extensively linked with chromosomal instability in addition to derangement of multiple tumor suppressors and oncoprotein regulated pathways. Therefore, the AURK family of kinases is a promising target for the treatment of various types of cancer. Over the past few decades, several potential inhibitors of AURK proteins have been identified and have reached various phases of clinical trials. But very few molecules have currently crossed the safety criteria due to their various toxic side effects. In the present study, we have adopted a computational polypharmacological strategy and identified four novel molecules that can target all three AURKs. These molecules were further investigated for their binding stabilities at the ATP binding pocket using molecular dynamics based simulation studies. The molecules selected adopting a multipronged computational approach can be considered as potential AURKs inhibitors for cancer therapeutics.

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Section: Resultsmentioning

confidence: 99%

Section: Structure-based Virtual Screening and Molecular Dockingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of polypharmacological anticancerous molecules against Aurora kinase family of proteins

Gupta

Kumar

Singh

et al. 2022

J of Cellular Biochemistry

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“…ASP 72 was considered as flexible residue) were used in the docking experiments. The molecular dynamic simulation of the protein-ligand complexes was performed using VMD-NAMD software with CHARMM forcefield and the 10 Å water layer parameters in all directions [ 51 ]. A total of 100,000 cycles of time steps were performed.…”

Section: Methodsmentioning

confidence: 99%

Combination Therapy of Ledipasvir and Itraconazole in the Treatment of COVID‐19 Patients Coinfected with Black Fungus: An In Silico Statement

Saha¹,

Yeom

Nimse

et al. 2022

BioMed Research International

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The manuscript mainly aimed at providing clues on improving the innate immunity of coronavirus patients and safeguarding them from both new mutant strains and black fungus infections. Coronavirus is readily mutating from one variant to another. Among the several variants, we selected SARS-CoV-2 B.1.1.7 in this study. Upon infection of any virus, ideally, the phagocytic cells of the host engulf and destroy the virus by a mechanism called phagocytosis. However, compromised immunity impairs phagocytosis, and thus, restoring the immune system is crucial for a speedy recovery of infected patients. The autophagy and activation of Toll-like receptor-4 are the only ways to restore innate immunity. Recently, immunocompromised COVID-19 patients have been suffering from the coinfection of black fungus. Rhizomucor, a black fungus species, causes more than 75% of cases of mucormycosis. Here, we present the results of molecular docking studies of sixty approved antiviral drugs targeting receptors associated with the SARS-CoV-2 B 1.1.7 variant (PDB id: 7NEH), activating the innate immune system (PDB id: 5YEC and 5IJC). We also studied the twenty approved antifungal drugs with Rhizomucor miehei lipase propeptide (PDB id: 6QPR) to identify the possible combination therapy for patients coinfected with coronavirus and black fungus. The ledipasvir showed excellent docking interactions with the 7NEH, 5YEC, and 5IJC, indicating that it is a perfect candidate for the treatment of COVID-19 patients. Itraconazole showed significant interaction with 6QPR of Rhizomucor miehei, suggesting that itraconazole can treat black fungus infections. In conclusion, the combination therapy of ledipasvir and itraconazole can be a better alternative for treating COVID-19 patients coinfected with black fungus.

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Tin (IV) chloride catalyzed one‐pot synthesis, characterization, and docking studies of 4‐aminoquinoline derivatives as Myt1 inhibitors

Muddagoni

Dasari

Bathula

et al. 2022

Journal of Heterocyclic Chem

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An efficient and practical method for the series of 4‐aminoquinoline derivatives has been developed via Tin (lV) chloride catalyzed cascade cyclization from 2‐aminobenzonitrile and different acetophenones. These novel chemical entities were characterized by their 1HNMR, 13CNMR spectra and high‐resolution mass spectrometer (HRMS) with their docking studies were performed to identify potential inhibitors of Myt1kinase protein. The synthesized analogs 3a–3l were docked with Myt1 kinase protein. Among these 3c, 3f, and 3g were showing promising Glide score, prime‐MMGBSA and ADME properties similar to Neratinib, Pelitinib cancer inhibiting drugs of Myt1 kinase protein. The amino acid ASP251of Myt1 kinase protein was consistently binding to novel chemical entities and existing drugs, indicating that the amino acid is crucial and responsible for its inhibition. Docking studies revealed that the compounds 3c, 3f, and 3g indicates that they can act as strong inhibitors of Myt1 kinase protein as that of comparable existing drugs Neratinib, Pelitinib.

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Identification of potential Aurora kinase-C protein inhibitors: an amalgamation of energy minimization, virtual screening, prime MMGBSA and AutoDock

Cited by 16 publications

References 54 publications

Identification of polypharmacological anticancerous molecules against Aurora kinase family of proteins

Identification of polypharmacological anticancerous molecules against Aurora kinase family of proteins

Combination Therapy of Ledipasvir and Itraconazole in the Treatment of COVID‐19 Patients Coinfected with Black Fungus: An In Silico Statement

Tin (IV) chloride catalyzed one‐pot synthesis, characterization, and docking studies of 4‐aminoquinoline derivatives as Myt1 inhibitors

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