TY - JOUR
T1 - In silico evaluation of 4-thiazolidinone-based inhibitors against the receptor for advanced glycation end products (RAGE)
AU - Haque, Ashanul
AU - Alenezi, Khalaf M.
AU - Khan, Mohd Wajid A.
AU - Soury, Raoudha
AU - Khan, Muhammad S.
AU - Ahamad, Shahzaib
AU - Ahmad, Shahnawaz
AU - Gupta, Dinesh
N1 - Publisher Copyright:
© 2023 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2023
Y1 - 2023
N2 - Non-enzymatic glycation of biomolecules by reducing sugars led to several products, including the advanced glycation end products (AGEs), the accumulation of which has been linked to various life-threatening diseases. The binding of AGEs to their respective protein receptors for advanced glycation end products (RAGE) can initiate a cascade of reactions, which may alter physiological conditions. The present work investigates the potential of 4-thiazolidinones as RAGE inhibitors. We performed an extensive computational study to identify the structural requirements needed to act as RAGE inhibitors. To achieve this goal, 4-thiazolidinone-based compounds available in PubChem, ZINC15, ChEMBL, and ChEBI databases were screened against RAGE (PDB: 4LP5), leading to the identification of top five drug-like candidates with a high binding affinity to RAGE V‐domain catalytic region. Drug likeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the top-scoring compounds have been studied and discussed. Global molecular descriptors, chemical reactivity, hardness, softness, etc., have been estimated. Finally, molecular dynamics (MD) simulations at 100 ns were carried out to check the stability and other properties. Overall, we believe that the identified compounds can potentially attenuate RAGE–AGE interactions. Communicated by Ramaswamy H. Sarma.
AB - Non-enzymatic glycation of biomolecules by reducing sugars led to several products, including the advanced glycation end products (AGEs), the accumulation of which has been linked to various life-threatening diseases. The binding of AGEs to their respective protein receptors for advanced glycation end products (RAGE) can initiate a cascade of reactions, which may alter physiological conditions. The present work investigates the potential of 4-thiazolidinones as RAGE inhibitors. We performed an extensive computational study to identify the structural requirements needed to act as RAGE inhibitors. To achieve this goal, 4-thiazolidinone-based compounds available in PubChem, ZINC15, ChEMBL, and ChEBI databases were screened against RAGE (PDB: 4LP5), leading to the identification of top five drug-like candidates with a high binding affinity to RAGE V‐domain catalytic region. Drug likeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the top-scoring compounds have been studied and discussed. Global molecular descriptors, chemical reactivity, hardness, softness, etc., have been estimated. Finally, molecular dynamics (MD) simulations at 100 ns were carried out to check the stability and other properties. Overall, we believe that the identified compounds can potentially attenuate RAGE–AGE interactions. Communicated by Ramaswamy H. Sarma.
KW - 4-thiazolidinones
KW - docking
KW - MD simulation
KW - MM-GBSA
KW - Receptor for advanced glycation end products
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U2 - 10.1080/07391102.2023.2290621
DO - 10.1080/07391102.2023.2290621
M3 - Article
C2 - 38063048
AN - SCOPUS:85179924198
SN - 0739-1102
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
ER -