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Journal : VALENSI

A Novel Benzenesulfonylurea-Substituted Pyridazinone Derivative with Antidiabetic Effect as the Peroxisome Proliferator-activated Receptor (PPAR-γ) Agonist Fatisa, Yuni; Yasthophi, Arif; Elviyenti, Elviyenti; Ikhtiaruddin, Ihsan; Frimayanti, Neni; Teruna, Hilwan Yuda; Jasril, Jasril
Jurnal Kimia Valensi Jurnal Kimia VALENSI, Volume 11, No. 1, May 2025
Publisher : Department of Chemistry, Faculty of Science and Technology Syarif Hidayatullah Jakarta State Islamic University

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15408/jkv.v11i1.42187

Abstract

Peroxisome Proliferator-activated Receptor (PPAR-γ) protein is one of the target proteins for insulin sensitivity therapy in Type 2 DM. PPAR-γ has a key role as a nuclear receptor that regulates the expression of several metabolism-related genes. This research aims to   synthesize a novel   benzenesulfonylurea-substituted   pyridazinone     derivative, namely (E)-N'-(1-(4-(3-(4-methoxyphenyl)-6-oxopyridazin-1(6H)- yl)phenyl)ethylidene)-4-methylbenzenesulfonohydrazide (8) and predicted it activity as the PPAR-γ agonist using a molecular docking approach and ADMET profiles. The compound 8 was obtained through a Schiff base condensation reaction between compound 6, p-tosyl hydrazine, and a glacial acetic acid catalyst using monowave. The purity of the compound was determined by TLC test, and melting point measurement. The structure was confirmed through FTIR, 1H-NMR, C-NMR and HRMS analysis. Molecular docking studies were carried out on the crystal structure of the human PPAR-γ Ligand Binding Domain target protein in complex with the α-aryloxyphenyl acetic acid agonist (PDB ID 1ZEO). The results of the docking show that compound 8 has a lower binding free energy than rosiglitazone (positive control) with a free energy value (S score) = -13.513 kcal/mol and -8.3089 kcal/mol, respectively. Compound 8 can form two hydrogen bonds with residues His323 and Ser289, π-π interactions with Phe363 and π-H interactions with Cys285.  The interactions are similar to the interaction between the native ligand agonists α-aryloxyphenyl acetic acid and rosiglitazone with the target protein. Furthermore, compound 8 is predicted to have a moderate ADME profile. The results support that compound 8 can be developed as a PPAR-γ agonist candidate for the antidiabetic therapeutic agent.
Co-Authors Abdi Wira Septama Abdi Wira Septama Abdi Wira Septama Adel Zamri Adel Zamri Adel Zamri Adel Zamri Adel Zamri Adel Zamri Adel Zamri Adel Zamri Adel Zamri Adel Zamri Adel zamri adli husin, Raja agistia, nesa Agustini, Tiara Tri alhamdania Balqis, Salsabila Alifah Nurul Khusnah Amanda, Denisya Amrina Rossada Septilapani Anabesi, Mazaya Putri Anfasa Mashudi, Fristio Anggraeni, Ica Winanda Anggraini, Haryeni Sastra Anita Lukman Antasya, Vaylia Armon Fernando Arsad, Larasati Aulia Wibowo, Selvi Azela, Lala Azlin, Kiranti Bella Parina, Ana BENNI ISKANDAR Daniel Sialagan Dea Dwi Putri Difa, Faradini Ramsanjami Efendi, Apriyani Eka Marisa Putri Elsa Etavianti Elsa Natia Elvi Khairani, Mai Elviyenti, Elviyenti Emma Susanti Enda Mora Etavianti, Elsa Fatmalia, Anggun Ferdy Firmansya Ferdy Firmansyah Fikri Maulana Fikri Maulana, Fikri Fina Aryani, Fina Fitriani, R. Rizatita Fitriani, Rizda Fri Murdiya, Fri Furi, Mustika Guntur Guntur Haiyul Fadhli Hamzah, Hasyrul Hendra, Rudi Herfindo, Nofal Herfindo, Noval Hery Widijanto Hilwan Y. Teruna Hilwan Yuda Teruna Husnawati Husnawati Ihsan Ikhtiarudin Ikhtiaruddin, Ihsan Irfan Maulana, Irfan Iriani, Revy Jasril , Jasril Jasril Jasril Kirana, Fharisti Kurniawan Putri, Nurafika Livia Nathania Meiriza Djohari, Meiriza Melzi Octaviani Meri Ernilawati Meridona Mira Febrina, Mira Muharani, Siska Muhtadi, Wildan Khairi Musyirna Rahmah Nasution Muttaqin, Fauzan Zein Nahdiah Nahdiah Nahdiah Nahdiah, Nahdiah Nasution, Musyirna Rahmah Nelly Oscifiani Nelly Oscifiani Ningsih, Yozi Fiedya Nofriyanti Nova Tantri Silalahi Noval Herfindo Noval Herfindo Noval Herfindo Noval Herfindo Noval Herfindo Noval Herfindo Novrianti, Nisa Nurul fadillah, Nurul Nurul Susianti Oscifiani, Nelly Panjaitan, Pretty Farida Peng-Wei, Ching Putri Rizki Rahmadani Putri, Monica Rifa Putri, Nadila Qurnia Pratiwi, Putri Rabiatul Adawiyah Rahayu Rahayu Rahayu Rahayu Rahayu Rahayu Rahayu Utami Rahim, Fatma Rahma Dona Rahma Dona, Rahma Rahmah, Rizka I’zaa Ramadhani, Nadea Zahra Ricardo, Nadira Atiqah Rickha Octavia Rindiyani Rindiyani Riska Prasetiawati Rizki Anugrah Rizki, Mulia Rohim, Muhammad Rosnita Dewi Rahmawati Rossi Passarella Ruska, Shinta Liana Rusnedy, Rahmayati S.Farm., M.Farm., Apt, Sondang Khairani Safitri, Ramanda Salsabila, Aulia Salsabillah, Mutiara Sari, Rinita Shafira Melsonia Silalahi, Nova Tantri Siregar, Lisa Andriyani Sisilawati, Kolista Sitanggang, Sarah Dianora Solihin, Tabah Teguh Utama Tria Harlianti Ulfa, Rodhia Vasmawati, Della Vella kurnia Wahyuni Veza Azteria viola Afrilizetira, Garnis Wahyuni, Dilla Widya Ari Sandi Winda Yusma Ameliah Wulandari, Zertiks Yasthophi, Arif Yueflen, Fadiyah Yuli Haryani Yum Eryanti Yum Eryanti Yum Eryanti Yuni Fatisa Yuri Amalia, Annisa Zafarani, Welly Zahirah Ananda, Salsabila