TY - JOUR
T1 - Synthesis, spectroscopic characterization, DFT and molecular docking of N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) naphthalene-1-sulfonamide derivatives
AU - Ashraf, Sajda
AU - Iqbal, Shazia
AU - Sebhaoui, Jihad
AU - Ozcan, Mehmet
AU - Kim, Woonghee
AU - Belmen, Burcu
AU - Yeşilyurt, Güldeniz
AU - Hanashalshahaby, Essam
AU - Zhang, Cheng
AU - Uhlen, Mathias
AU - Boren, Jan
AU - Turkez, Hasan
AU - Mardinoglu, Adil
N1 - Publisher Copyright:
© 2024
PY - 2024/9/15
Y1 - 2024/9/15
N2 - Liver pyruvate kinase (PKL) is a key player in controlling metabolic pathways and ATP production within the liver's glycolysis pathway. Since PKL modulators have been identified as a promising target for treating hepatocellular carcinoma (HCC) and non-alcoholic fatty liver disease (NAFLD), our research is centered on the development and synthesis of derivatives of N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) naphthalene-1-sulfonamide with the aim of modulating PLK. To improve PKL specificity, we used structural analysis and modeling as a guide. Notably, compound PKL-05 became the series' only active ingredient. DFT, Hirshfeld surface analysis, and molecular docking were used in our study to thoroughly examine the connection between compound structures and their computational functions. The global hardness and softness energy values, as well as the HOMO-LUMO energy gap value, were computed in order to forecast the chemical reactivity of this newly synthesized molecule. These energy values indicate that this molecule tends to be chemically stable and has little chemical reactivity. The results demonstrated a strong agreement between theoretical forecasts and experimental findings. In particular, PKL-05 exhibits encouraging traits that establish it as a useful starting point for additional research in the search for innovative PKL modulators to tackle the treatment issues associated with NAFLD and HCC.
AB - Liver pyruvate kinase (PKL) is a key player in controlling metabolic pathways and ATP production within the liver's glycolysis pathway. Since PKL modulators have been identified as a promising target for treating hepatocellular carcinoma (HCC) and non-alcoholic fatty liver disease (NAFLD), our research is centered on the development and synthesis of derivatives of N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) naphthalene-1-sulfonamide with the aim of modulating PLK. To improve PKL specificity, we used structural analysis and modeling as a guide. Notably, compound PKL-05 became the series' only active ingredient. DFT, Hirshfeld surface analysis, and molecular docking were used in our study to thoroughly examine the connection between compound structures and their computational functions. The global hardness and softness energy values, as well as the HOMO-LUMO energy gap value, were computed in order to forecast the chemical reactivity of this newly synthesized molecule. These energy values indicate that this molecule tends to be chemically stable and has little chemical reactivity. The results demonstrated a strong agreement between theoretical forecasts and experimental findings. In particular, PKL-05 exhibits encouraging traits that establish it as a useful starting point for additional research in the search for innovative PKL modulators to tackle the treatment issues associated with NAFLD and HCC.
KW - DFT
KW - Docking
KW - Hirschfield surface analysis
KW - Liver pyruvate kinase
KW - Synthesis
KW - X-ray
UR - http://www.scopus.com/inward/record.url?scp=85192494249&partnerID=8YFLogxK
U2 - 10.1016/j.molstruc.2024.138470
DO - 10.1016/j.molstruc.2024.138470
M3 - Article
AN - SCOPUS:85192494249
SN - 0022-2860
VL - 1312
JO - JOURNAL OF MOLECULAR STRUCTURE
JF - JOURNAL OF MOLECULAR STRUCTURE
M1 - 138470
ER -
