CD Tesis

Sintesis Dan Uji Molecular Docking Senyawa Turunan Piridazinon Tersubtitusi N-Asetohidrazida Sebagai Antikanker Payudara

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SUMMARY
Putri Mar Atus Shalihah, NIM. 2210247899, Synthesis and Molecular Docking
Test of Pyridazinone Derivative Compounds Substituted with NAcetohydrazide
as Breast Anticancer, supervised by Jasril and Rudi Hendra.
Breast cancer remains one of the leading causes of death among women
worldwide. As a result, the search for new anticancer agents with high specificity
toward molecular targets continues. Among many organic compounds,
pyridazinones are one group of compounds with anticancer activity. Modifying
the structure of these compounds has the potential to enhance their biological
activity. In this study, the synthesis of N-acetohydrazide-substituted pyridazinone
derivatives was carried out, and their anticancer potential was evaluated in silico
through molecular docking tests against the c-kit tyrosine kinase receptor, an
enzyme that plays a crucial role in the proliferation and survival of cancer cells,
particularly in certain subtypes of breast cancer. The compound
2-(3-(3-methoxyphenyl)-6-oxopyridazin-1(6H)-yl) acetohydrazide (25a) and
2-(3-(3,4-dimethoxyphenyl)-6-oxopyridazin-1(6H)-yl)acetohydrazide (25b) were
successfully synthesised through three reaction steps involving condensation and
substitution reactions with yields of 48.14% and 52.80%, respectively. The purity
of the target compounds was analyzed using thin-layer chromatography (TLC),
melting point determination, and high-performance liquid chromatohraphy
(HPLC). The TLC and HPLC chromatograms exhibited a single spot and single
dominant peak for each compound indicating high purity. This finding was further
supported by melting point analysis, which demonstrated a narrow melting point
range of less than 2˚C confirming compound purity. Structural elucidation of the
synthesized compounds was performed using UV-Vis, Fourier-transform infrared
(FTIR), mass spectrometry (MS), proton nuclear magnetic resonance (1H-NMR),
and carbon-13 nuclear magnetic resonance (13C-NMR) spectroscopy. The
characterization results confirmed that the synthesized compounds corresponded
to the expected target structures. The biological activity of compounds 25a and
25b as C-kit tyrosine kinase inhibitors (PDB ID: 1T46) was evaluated through
moleculer docking studies using the MOE 2022.02. The docking results compared
doksorubisin as a reference inhibitor, demonstrated that compound 25b exhibited
the highest inhibitory potential eith a binding free energy of -10.09 kcal/mol and
the formation of three hydrogen bonds with amino acid residues Cys673, Lys623
and Asp810. However, the inhibitory activity of compound 25b remained inferior
to that of doksorubisin. Furthemore, an absorption, distribution, metabolism,
excretion, and toxicity (ADMET) study indicated that compound 25b complies
with Lipinski’s rule of five and possesses favorable drug like properties. These
finding suggest that N-acetohydrazide-subtituted pyridazinone derivatives warrant
further investigation as potential anticancer agent.
Keywords: breast anticancer, synthesis, pyridazinone, 1T46 receptor, molecular
docking, ADME profiling

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Ketersediaan

Informasi Detail

Judul Seri

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No. Panggil

2210247899

Penerbit

Pekanbaru. : Universitas Riau – PASCA– Magister Kimia., 2025

Deskripsi Fisik

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Bahasa

Indonesia

ISBN/ISSN

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Klasifikasi

2210247899

Tipe Isi

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Tipe Media

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Tipe Pembawa

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Edisi

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Subjek

MAGISTER KIMIA

Info Detail Spesifik

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Pernyataan Tanggungjawab

RIDHO

Versi lain/terkait

Lampiran Berkas

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