Molecular docking, ADME analysis, and pharmacophore modelling of benzoxazole fused azetidinone derivatives as antibreast cancer agents

Dheeraj, Gupta; Kumar, Pankaj; Apte, Kishori; Ashtekar, Harsha; Dixit, Seshagiri R

doi:10.54085/ap.2023.12.1.37

Cited by 2 publications

(1 citation statement)

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“…The QikProp module provides a star rating for each phytochemical based on ADME descriptors. Overall, fifty ADME descriptors were assessed, including cell permeability (pCaco-2 and pMDCK) and oral absorption (% human oral absorption), providing a star score; a lower number of stars indicates high drug-like properties [37]. In our case, the phytochemicals with a star score of less than five were selected for subsequent analysis.…”

Section: Adme Parametersmentioning

confidence: 99%

Network-Derived Radioresistant Breast Cancer Target with Candidate Inhibitors from Brown Algae: A Sequential Assessment from Target Selection to Quantum Chemical Calculation

Sivakumar,

Ahmad,

Emran

et al. 2023

Marine Drugs

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Despite significant progress in early detection and treatment, a few aggressive breast cancers still exhibit resistance to therapy. This study aimed to identify a therapeutic target for radioresistant breast cancer (RRbc) through a protein network from breast cancer genes and to evaluate potent phytochemicals against the identified target. Our approach includes the integration of differential expression genes from expression datasets to create a protein network and to use survival analysis to identify the crucial RRbc protein in order to discover a therapeutic target. Next, the phytochemicals sourced from brown algae were screened through molecular docking, ADME (absorption, distribution, metabolism, and excretion), molecular dynamics (MD) simulation, MM-GBSA, and quantum mechanics against the identified target. As a result of our protein network investigation, the proto-oncogene c-KIT (KIT) protein was identified as a potent radioresistant breast cancer target. Further, phytochemical screening establishes that nahocol-A1 from brown algae has high binding characteristics (−8.56 kcal/mol) against the KIT protein. Then, quantum chemical analysis of nahocol-A1 provided insights into its electronic properties favorable for protein binding. Also, MD simulation comprehends the conformational stability of the KIT–nahocol-A1 complex. Overall, our findings suggest nahocol-A1 could serve as a promising therapeutic candidate for radioresistant breast cancer.

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Section: Adme Parametersmentioning

confidence: 99%

Network-Derived Radioresistant Breast Cancer Target with Candidate Inhibitors from Brown Algae: A Sequential Assessment from Target Selection to Quantum Chemical Calculation

Sivakumar,

Ahmad,

Emran

et al. 2023

Marine Drugs

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Inhibition of β-lactamase by Novel Benzothiazole-Coupled Azetidinone Derivatives: A Comprehensive Study Using an In silico and In vitro Approaches Against Multi Drug Resistant Bacteria

Rajesh,

Koshy,

Akshay

et al. 2024

J. Comput. Biophys. Chem.

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Anti-microbial resistance has emerged as the leading cause of death worldwide with the rise of multidrug-resistant (MDR) bacteria, the need for novel anti-microbials to treat serious illnesses has become a great necessity. Hence, in this study, we aimed to design and synthesize benzothiazole-coupled azetidinone derivatives (GD1–GD12) as novel antibacterial agents. The synthesized compounds were elucidated by nuclear magnetic resonance, infrared and mass spectroscopy. The antibacterial activities of these compounds were tested against antibiotic-susceptible and MDR strains of bacteria. In addition, we performed ADME profiling, molecular docking and molecular dynamic simulations, principle component analysis, dynamic cross-correlation map and free-energy landscape to assess the binding of synthesized compounds with the [Formula: see text]-lactamase. Among the synthesized compounds GD6 and GD5 displayed minimum inhibitory concentrations of 12.5 [Formula: see text]g/mL and 50 [Formula: see text]g/mL against MDR strains of E. coli; more effective than standard. The molecular docking of designed molecules was performed against [Formula: see text]-lactamase enzyme and the stability of the complex was validated. The pharmacokinetic profile displayed the compounds to possess druggable properties within the suitable ranges. The in silico approach displayed compound GD6 to be stable with [Formula: see text]-lactamase enzyme; indicating the mechanism for these compounds to be via inhibition of [Formula: see text]-lactamase. The novel anti-microbial compounds assessed against susceptible and MDR strains of bacteria possess antibacterial potential via the inhibition of [Formula: see text]-lactamase. The aforementioned data will be crucial to the development of novel broad-spectrum antibacterial compounds.

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Molecular docking, ADME analysis, and pharmacophore modelling of benzoxazole fused azetidinone derivatives as antibreast cancer agents

Cited by 2 publications

References 0 publications

Network-Derived Radioresistant Breast Cancer Target with Candidate Inhibitors from Brown Algae: A Sequential Assessment from Target Selection to Quantum Chemical Calculation

Network-Derived Radioresistant Breast Cancer Target with Candidate Inhibitors from Brown Algae: A Sequential Assessment from Target Selection to Quantum Chemical Calculation

Inhibition of β-lactamase by Novel Benzothiazole-Coupled Azetidinone Derivatives: A Comprehensive Study Using an In silico and In vitro Approaches Against Multi Drug Resistant Bacteria

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