scholarly journals Beyond Traditional Structure-Based Drug Design: The Role of Iron Complexation, Strain, and Water in the Binding of Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylase 2

ACS Omega ◽  
2019 ◽  
Vol 4 (4) ◽  
pp. 6703-6708
Author(s):  
Scott D. Bembenek ◽  
Hariharan Venkatesan ◽  
Hillary M. Peltier ◽  
Mark D. Rosen ◽  
Terrance D. Barrett ◽  
...  
Keyword(s):  
Drug Design ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Structure Based Drug Design ◽  
Traditional Structure ◽  
Iron Complexation

scholarly journals Systematic review on role of structure based drug design (SBDD) in the identification of anti-viral leads against SARS-Cov-2

2021 ◽  
Vol 2 ◽  
pp. 100026
Author(s):  
Nilesh Gajanan Bajad ◽  
Swetha Rayala ◽  
Gopichand Gutti ◽  
Anjali Sharma ◽  
Meenakshi Singh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Drug Design ◽  
Structure Based Drug Design

The role of quantum mechanics in structure-based drug design

2007 ◽  
Vol 12 (17-18) ◽  
pp. 725-731 ◽  
Author(s):  
Kaushik Raha ◽  
Martin B. Peters ◽  
Bing Wang ◽  
Ning Yu ◽  
Andrew M. Wollacott ◽  
...  
Keyword(s):  
Quantum Mechanics ◽  
Drug Design ◽  
Structure Based Drug Design

scholarly journals Repurposing combination therapy of Voacamine with Vincristine for down regulation of HIF-1α/FASN co-axis and PHD2 activation in ER+ mammary neoplasia

2020 ◽  
Author(s):  
Lakhveer Singh ◽  
Manjari Singh ◽  
Dinesh Kumar ◽  
Mohd. Nazam Ansari ◽  
Abdulaziz S. Saeedan ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Combination Therapy ◽  
Fatty Acid Synthase ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Over Expression ◽  
Hypoxia Inducible Factor 1Α ◽  
Gland Carcinoma

Abstract Background The current study was attempted to inquest the role of combination therapy of Voacamine and Vincristine for the prevention of mammary gland carcinoma through prolyl hydroxylase-2 activation. The prolyl hydroxylase‐2 activation leads the downregulation of hypoxia‐inducible factor‐1α and fatty acid synthase. Over expression of hypoxia inducible factor-1α and fatty acid synthase is previously reported in solid tumor of mammary gland. Methods After screening a battery of natural compounds which were similar to vincristine, vocamine was selected as a possible prolyl hydroxylase-2 activator and justify its activity using 7, 12-Dimethylbenz[a]anthracene induced rat model. The combination therapy was evaluated for cardiac toxicity using hemodynamic profile. The angiogenic markers were evaluated using carmine staining. Monotherapy and combination therapy were also evaluated for liver and kidney toxicity through haematoxylin and eosin staining. The combination therapy also delineated the markers of oxidative stress favorably. Afterwards, the disruption of fatty acids was evaluated using gas chromatography. Results The immunoblotting analysis validated that combination therapy has a potential to switch on the prolyl hydroxylase-2 activity and thus initiate proteolytic degradation of hypoxia‐inducible factor‐1α and its consequence effects. The combination therapy also stimulated programmed cell death (apoptosis) in rapidly dividing cancer cells. Conclusion The present study explores the role of voacamine in activation of prolyl hydroxylase-2 which can decrease over expression of hypoxia‐inducible factor‐1α and fatty acid synthase in cells of mammary gland carcinoma.

scholarly journals Repurposing Combination Therapy of Voacamine with Vincristine for Down Regulation of HIF-1α/FASN Co-Axis and PHD2 Activation in ER+ Mammary Neoplasia

2020 ◽  
Author(s):  
Lakhveer Singh ◽  
Manjari Singh ◽  
Mohd. Nazam Ansari ◽  
Abdulaziz S. Saeedan ◽  
Gaurav Kaithwas
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Combination Therapy ◽  
Fatty Acid Synthase ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Over Expression ◽  
Hypoxia Inducible Factor 1Α ◽  
Gland Carcinoma

Abstract Background: The current study was attempted to inquest the role of combination therapy of Voacamine and Vincristine for the prevention of mammary gland carcinoma through prolyl hydroxylase‐2 activation. The prolyl hydroxylase‐2 activation leads the downregulation of hypoxia‐inducible factor‐1α and fatty acid synthase. Over expression of hypoxia inducible factor-1α and fatty acid synthase is previously reported in solid tumor of mammary gland. Methods: After screening a battery of natural compounds which were similar to vincristine, vocamine was selected as a possible prolyl hydroxylase‐2 activator and justify its activity using 7, 12-Dimethylbenz[a]anthracene induced rat model. The combination therapy was evaluated for cardiac toxicity using hemodynamic profile. The angiogenic markers were evaluated using carmine staining. Monotherapy and combination therapy were also evaluated for liver and kidney toxicity through haematoxylin and eosin staining. The combination therapy also delineated the markers of oxidative stress favorably. Afterwards, the disruption of fatty acids was evaluated using gas chromatography. Results: The immunoblotting analysis validated that combination therapy has a potential to switch on the prolyl hydroxylase‐2 activity and thus initiate proteolytic degradation of hypoxia‐inducible factor‐1α and its consequence effects. The combination therapy also stimulated programmed cell death (apoptosis) in rapidly dividing cancer cells.Conclusion: The present study explores the role of voacamine in activation of prolyl hydroxylase‐2 which can decrease over expression of hypoxia‐inducible factor‐1α and fatty acid synthase in cells of mammary gland carcinoma.

scholarly journals Recent Trends and Applications of Molecular Modeling in GPCR–Ligand Recognition and Structure-Based Drug Design

2018 ◽  
Vol 19 (7) ◽  
pp. 2105 ◽  
Author(s):  
Xiaojing Yuan ◽  
Yechun Xu
Keyword(s):  
Molecular Modeling ◽  
Drug Design ◽  
Ligand Recognition ◽  
Energy Calculation ◽  
Enhanced Sampling ◽  
Structure Based Drug Design ◽  
Recent Trends ◽  
Indispensable Tool ◽  
G Protein Coupled

G protein-coupled receptors represent the largest family of human membrane proteins and are modulated by a variety of drugs and endogenous ligands. Molecular modeling techniques, especially enhanced sampling methods, have provided significant insight into the mechanism of GPCR–ligand recognition. Notably, the crucial role of the membrane in the ligand-receptor association process has earned much attention. Additionally, docking, together with more accurate free energy calculation methods, is playing an important role in the design of novel compounds targeting GPCRs. Here, we summarize the recent progress in the computational studies focusing on the above issues. In the future, with continuous improvement in both computational hardware and algorithms, molecular modeling would serve as an indispensable tool in a wider scope of the research concerning GPCR–ligand recognition as well as drug design targeting GPCRs.

scholarly journals Metabolic N-Dealkylation and N-Oxidation as Elucidators of the Role of Alkylamino Moieties in Drugs Acting at Various Receptors

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1917
Author(s):  
Babiker M. EH-Haj
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
Physicochemical Properties ◽  
Open Chain ◽  
Structure Based Drug Design ◽  
Receptor Selectivity ◽  
Drug Molecules ◽  
Metabolic Reactions ◽  
Insight Into

Metabolic reactions that occur at alkylamino moieties may provide insight into the roles of these moieties when they are parts of drug molecules that act at different receptors. N-dealkylation of N,N-dialkylamino moieties has been associated with retaining, attenuation or loss of pharmacologic activities of metabolites compared to their parent drugs. Further, N-dealkylation has resulted in clinically used drugs, activation of prodrugs, change of receptor selectivity, and providing potential for developing fully-fledged drugs. While both secondary and tertiary alkylamino moieties (open chain aliphatic or heterocyclic) are metabolized by CYP450 isozymes oxidative N-dealkylation, only tertiary alkylamino moieties are subject to metabolic N-oxidation by Flavin-containing monooxygenase (FMO) to give N-oxide products. In this review, two aspects will be examined after surveying the metabolism of representative alkylamino-moieties-containing drugs that act at various receptors (i) the pharmacologic activities and relevant physicochemical properties (basicity and polarity) of the metabolites with respect to their parent drugs and (ii) the role of alkylamino moieties on the molecular docking of drugs in receptors. Such information is illuminative in structure-based drug design considering that fully-fledged metabolite drugs and metabolite prodrugs have been, respectively, developed from N-desalkyl and N-oxide metabolites.

scholarly journals Computer Aided Drug Designing

2017 ◽  
Vol 6 (1) ◽  
pp. 1433
Author(s):  
Vijay Kumar Sehgal ◽  
Supratik Das ◽  
Anand Vardhan
Keyword(s):  
Drug Design ◽  
Medical Science ◽  
Quantitative Structure ◽  
Structure Property ◽  
Structure Based Drug Design ◽  
Safety Issues ◽  
Computer Aided ◽  
Drug Designing ◽  
Quantitative Structure Property Relationships

Designing of drugs and their development are a time and resource consuming process. There is an increasing effort to introduce the role of computational approach to chemical and biological space in order to organise the design and development of drugs and their optimisation. The role of Computer Aided Drug Designing (CADD) are nowadays expressed in Nanotechnology, Molecular biology, Biochemistry etc. It is a diverse discipline where various forms of applied and basic researches are interlinked with each other. Computer aided or in Silico drug designing is required to detect hits and leads. Optimise/ alter the absorption, distribution, metabolism, excretion and toxicity profile and prevent safety issues. Some commonly used computational approaches include ligand-based drug design, structure-based drug design, and quantitative structure-activity and quantitative structure-property relationships. In today's world, due to an avid interest of regulatory agencies and, even pharmaceutical companies in advancing drug discovery and development process by computational means, it is expected that its power will grow as technology continues to evolve. The main purpose of this review article is to give a brief glimpse about the role Computer Aided Drug Design has played in modern medical science and the scope it carries in the near future, in the service of designing newer drugs along with lesser expenditure of time and money.

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