Novel nitrogen-containing heterocyclic compounds in GPR109A as an anti-hyperlipidemic: Homology modeling, docking, dynamic simulation studies

Asha Thomas

Makale detayları

Novel nitrogen-containing heterocyclic compounds in GPR109A as an anti-hyperlipidemic: Homology modeling, docking, dynamic simulation studies

Yazarlar:

Asha Thomas

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.24 Issue 4, pp.452-463

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347932

pISSN:

2630-6344

Anahtar kelimeler:

Özet:

 Niacin or nicotinic acid therapy leads to reduction of the level of Low-density Lipoprotein cholesterol 20-40 with significant elevation of High-Density Lipopreoin cholesterol level 20-35. From research, it was said that Nicotinic acid might exert its positive action by activating the G-protein-coupled receptor GPCR which is found on adipocytes. GPR109A family of GPCR receptor was important for nicotinic acid niacin for its anti-lipolytic effects. As GPR109A is a targeted receptor for the treatment of dyslipidemia, its structural analysis needs to be elucidated. But the Protein 3D structure of target was not available at Protein Data Bank PDB, so we have generated its structure through homology modeling and validation was carried out. Screening of top lead molecules with the help of various computational approaches like molecular-docking and molecular dynamic MD simulations studies with different online tools were carried out. The docking results showed that the lead compound 2B R-methyl 2-2- 1H-indol-3-yl acetamido-3-1H-indol-3-yl propionate revealed significant binding energy value -30.54 kcalmol as that with the nicotinic acid which is a standard drug -17.68 kcalmol. In addition to that, Molecular-Dynamic MD simulations analysis proved that compound 2B has lesser variations throughout the simulation period as represented by the root-mean-square deviation RMSD and root-mean-square fluctuation RMSF graphs. Current in silico study describes the modeling of novel heterocyclic compounds as antihyperlipidemic drugs for the treatment of dyslipidemia. This study also describes a deeper idea about the structural information of the lead compound 2B and its entire molecular interactions against GPCR109A and provides a hypothetical guideline to utilize this compound as an antihyperlipidemic for the treatment of dyslipidemia.

 Niacin or nicotinic acid therapy leads to reduction of the level of Low-density Lipoprotein cholesterol 20-40 with significant elevation of High-Density Lipopreoin cholesterol level 20-35. From research, it was said that Nicotinic acid might exert its positive action by activating the G-protein-coupled receptor GPCR which is found on adipocytes. GPR109A family of GPCR receptor was important for nicotinic acid niacin for its anti-lipolytic effects. As GPR109A is a targeted receptor for the treatment of dyslipidemia, its structural analysis needs to be elucidated. But the Protein 3D structure of target was not available at Protein Data Bank PDB, so we have generated its structure through homology modeling and validation was carried out. Screening of top lead molecules with the help of various computational approaches like molecular-docking and molecular dynamic MD simulations studies with different online tools were carried out. The docking results showed that the lead compound 2B R-methyl 2-2- 1H-indol-3-yl acetamido-3-1H-indol-3-yl propionate revealed significant binding energy value -30.54 kcalmol as that with the nicotinic acid which is a standard drug -17.68 kcalmol. In addition to that, Molecular-Dynamic MD simulations analysis proved that compound 2B has lesser variations throughout the simulation period as represented by the root-mean-square deviation RMSD and root-mean-square fluctuation RMSF graphs. Current in silico study describes the modeling of novel heterocyclic compounds as antihyperlipidemic drugs for the treatment of dyslipidemia. This study also describes a deeper idea about the structural information of the lead compound 2B and its entire molecular interactions against GPCR109A and provides a hypothetical guideline to utilize this compound as an antihyperlipidemic for the treatment of dyslipidemia.

 Niacin or nicotinic acid therapy leads to reduction of the level of Low-density Lipoprotein cholesterol 20-40 with significant elevation of High-Density Lipopreoin cholesterol level 20-35. From research, it was said that Nicotinic acid might exert its positive action by activating the G-protein-coupled receptor GPCR which is found on adipocytes. GPR109A family of GPCR receptor was important for nicotinic acid niacin for its anti-lipolytic effects. As GPR109A is a targeted receptor for the treatment of dyslipidemia, its structural analysis needs to be elucidated. But the Protein 3D structure of target was not available at Protein Data Bank PDB, so we have generated its structure through homology modeling and validation was carried out. Screening of top lead molecules with the help of various computational approaches like molecular-docking and molecular dynamic MD simulations studies with different online tools were carried out. The docking results showed that the lead compound 2B R-methyl 2-2- 1H-indol-3-yl acetamido-3-1H-indol-3-yl propionate revealed significant binding energy value -30.54 kcalmol as that with the nicotinic acid which is a standard drug -17.68 kcalmol. In addition to that, Molecular-Dynamic MD simulations analysis proved that compound 2B has lesser variations throughout the simulation period as represented by the root-mean-square deviation RMSD and root-mean-square fluctuation RMSF graphs. Current in silico study describes the modeling of novel heterocyclic compounds as antihyperlipidemic drugs for the treatment of dyslipidemia. This study also describes a deeper idea about the structural information of the lead compound 2B and its entire molecular interactions against GPCR109A and provides a hypothetical guideline to utilize this compound as an antihyperlipidemic for the treatment of dyslipidemia.

 Niacin or nicotinic acid therapy leads to reduction of the level of Low-density Lipoprotein cholesterol 20-40 with significant elevation of High-Density Lipopreoin cholesterol level 20-35. From research, it was said that Nicotinic acid might exert its positive action by activating the G-protein-coupled receptor GPCR which is found on adipocytes. GPR109A family of GPCR receptor was important for nicotinic acid niacin for its anti-lipolytic effects. As GPR109A is a targeted receptor for the treatment of dyslipidemia, its structural analysis needs to be elucidated. But the Protein 3D structure of target was not available at Protein Data Bank PDB, so we have generated its structure through homology modeling and validation was carried out. Screening of top lead molecules with the help of various computational approaches like molecular-docking and molecular dynamic MD simulations studies with different online tools were carried out. The docking results showed that the lead compound 2B R-methyl 2-2- 1H-indol-3-yl acetamido-3-1H-indol-3-yl propionate revealed significant binding energy value -30.54 kcalmol as that with the nicotinic acid which is a standard drug -17.68 kcalmol. In addition to that, Molecular-Dynamic MD simulations analysis proved that compound 2B has lesser variations throughout the simulation period as represented by the root-mean-square deviation RMSD and root-mean-square fluctuation RMSF graphs. Current in silico study describes the modeling of novel heterocyclic compounds as antihyperlipidemic drugs for the treatment of dyslipidemia. This study also describes a deeper idea about the structural information of the lead compound 2B and its entire molecular interactions against GPCR109A and provides a hypothetical guideline to utilize this compound as an antihyperlipidemic for the treatment of dyslipidemia.

Makale detayları

Novel nitrogen-containing heterocyclic compounds in GPR109A as an anti-hyperlipidemic: Homology modeling, docking, dynamic simulation studies

Yazarlar:

Asha Thomas

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.24 Issue 4, pp.452-463

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347932

pISSN:

2630-6344

G-protein coupled receptor (GPCR)

homology modeling

antihyperlipidemic drugs

nicotinic acid

molecular docking and molecular dynamic simulations

Sayı

Makale detayları

Novel nitrogen-containing heterocyclic compounds in GPR109A as an anti-hyperlipidemic: Homology modeling, docking, dynamic simulation studies

Yazarlar: Asha Thomas

Yayıncı: Marmara University

Ana Başlıklar: Pharmaceutical Chemistry

Dergi: Journal of Research in Pharmacy Vol.24 Issue 4, pp.452-463

Belge Tipi: Makale

Yayın Tarihi: 6/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001347932

pISSN: 2630-6344

G-protein coupled receptor (GPCR)

homology modeling

antihyperlipidemic drugs

nicotinic acid

molecular docking and molecular dynamic simulations

Sayı

Yazarlar:

Asha Thomas

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.24 Issue 4, pp.452-463

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347932

pISSN:

2630-6344