CD Tesis

Sintesis, Studi Molecular Docking Dan Uji Aktivitas Inhibisi Enzim Tirosinase Senyawa Turunan Pirazolo[4.3c]Piridin

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Tyrosinase is an enzyme that plays an important role in synthesis of
melanin through a process called melagonesis. Excessive expression of melanin
causes hyperpigmentation of human skin, including browning of fruits, thereby
reducing its economic value. The aimsof this study are to screen for tyrosinase
inhibitors by synthesizing halogen-substituted pyrazolo-pyridine derivatives.
Furthermore, the compound will be evaluated for its inhibitory activity against the
tyrosinase enzyme through molecular docking studies and in vitro testing of the
fungus Agaricus bisporus tyrosinase enzyme. The pyrazolo-pyridine compound
was obtained through two-steps synthesis. First, the intermediate compound,
namely curcumin, a derivative of 3,5-bis(arylidiene)-4-piperidone, was
synthesized through the Cleisen-Schmidt condensation reaction of 4-piperidone
derivatives and aromatic benzaldehyde. Furthermore, the curcumin intermediate
was reacted with phenylhydrazine through a cyclocondensation reaction to
produce(E)-7-(4-chlorobenzylidene)-3-(4-chlorophenyl)-5-methyl-2-phenyl-
3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine (20) and (E)-5-benzyl-7-(3-
bromobenzylidene)-3-(3-bromophenyl)-2-phenyl-3,3a,4,5,6,7-hexahydro-2Hpyrazolo[
4,3-c]pyridine (21)as a target compounds. Then molecular docking
study was carried out using Molecular Operating Environment (MOE) 2020.0901
program on the active site of the fungal tyrosinase enzyme Agaricus bisporus
bound to tropolon (ID: 2Y9X), while in vitro tests were carried out on the same
tyrosinase enzyme using a spectrophotometric method by detecting the presence
of dopachrome in wavelength of 492 nm.
In the synthesis stage, pyrazolo-pyridine derivatives 20 and 21 have been
successfully synthesized with yields of 7% and 11%, respectively. The chemical
structure of the target compound was identified through interpretation of UV,
FTIR, NMR and HRMS spectra. The results of molecular docking showed that
both compounds had lower binding free energy values than the positive control,
kojic acid. Compounds 20 and 21 have a binding free energy value of -8.7
kcal/mol and -6.4 kcal/mol, respectively. Kojic acid has an energy of -5.23
kcal/mol. However, the results of in vitro tests on the tyrosinase enzyme showed
that 20 compounds had slightly better activity than 21 compounds, with IC50
values of 380.4 M and > 500 M. However, this value is still much higher than
kojic acid, so it is considered inactive.
Keywords: Hyperpigmentation, melanin, molecular docking, pyrazolo-pyridine,
and tyrosinase

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Ketersediaan

Informasi Detail

Judul Seri

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No. Panggil

10 05. 221 (0006)

Penerbit

Pekanbaru : Universitas Riau – Pascasarjana – Tesis Kimia., 2021

Deskripsi Fisik

xiii, 77 hlm.: ill.: 29 cm

Bahasa

Indonesia

ISBN/ISSN

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Klasifikasi

10 05. 221 (0006)

Tipe Isi

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Tipe Media

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Tipe Pembawa

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Edisi

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Subjek

KIMIA

Info Detail Spesifik

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Pernyataan Tanggungjawab

FATAH

Versi lain/terkait

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