Synthesis, spectroscopic characterization, DFT and molecular docking of N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) naphthalene-1-sulfonamide derivatives

Ashraf, SajdaaTrustlife Labs Drug Research & Development Center, 34774 Istanbul, Turkiye (författare)

QC 20240620
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.

Iqbal, ShaziaaTrustlife Labs Drug Research & Development Center, 34774 Istanbul, Turkiye (författare)
Sebhaoui, JihadaTrustlife Labs Drug Research & Development Center, 34774 Istanbul, Turkiye (författare)
Özcan, MehmetKTH,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1ilte0b (författare)
Kim, WoongheeKTH,Systembiologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1nic2pk (författare)
Belmen, BurcuaTrustlife Labs Drug Research & Development Center, 34774 Istanbul, Turkiye (författare)
Yeşilyurt, GüldenizaTrustlife Labs Drug Research & Development Center, 34774 Istanbul, Turkiye (författare)
Hanashalshahaby, EssamaTrustlife Labs Drug Research & Development Center, 34774 Istanbul, Turkiye (författare)
Zhang, ChengKTH,Systembiologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1ww5kvp (författare)
Uhlén, MathiasKTH,Systembiologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1dulvmw (författare)
Boren, JancDepartment of Molecular and Clinical Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden (författare)
Turkez, HasandDepartment of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum, Turkiye (författare)
Mardinoglu, AdilKTH,Systembiologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1t8kmr6 (författare)
aTrustlife Labs Drug Research & Development Center, 34774 Istanbul, TurkiyeScience for Life Laboratory, SciLifeLab (creator_code:org_t)

Av författaren/redakt...: Ashraf, Sajda; Iqbal, Shazia; Sebhaoui, Jihad; Özcan, Mehmet; Kim, Woonghee; Belmen, Burcu; visa fler...; Yeşilyurt, Gülde ...; Hanashalshahaby, ...; Zhang, Cheng; Uhlén, Mathias; Boren, Jan; Turkez, Hasan; Mardinoglu, Adil; visa färre...

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