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Cancer is a disease related to the abnormal growth of cell. The potency of <br /> <br /> <br /> <br /> porphyrin compounds as anticancer agents have already known due to their affinity <br /> <br /> <br /> <br /> to the DNA, however, the study...
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| Format: | Dissertations |
| Language: | Indonesia |
| Online Access: | https://digilib.itb.ac.id/gdl/view/27396 |
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| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | Cancer is a disease related to the abnormal growth of cell. The potency of <br />
<br />
<br />
<br />
porphyrin compounds as anticancer agents have already known due to their affinity <br />
<br />
<br />
<br />
to the DNA, however, the study about their interaction with the non-DNA target is <br />
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<br />
<br />
still limited. The purpose of present research was to obtain porphyrin derivatives <br />
<br />
<br />
<br />
as a candidate of anticancer and information about their interaction to the non- <br />
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<br />
<br />
DNA target. Five known porphyrin derivatives and three novel porphyrin <br />
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derivatives bearing bis(3,4-ethylcarboxymethylenoxy) phenyl (BECP) as mesosubstituent were used to study their interaction with their targets (in silico study), <br />
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<br />
<br />
synthesized, and tested their cytotoxicity activity against cancer cell line. Three <br />
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novel porphyrins with meso-susbituent of BECP were designed as candidates of <br />
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radiopharmaceutical ligand and their interactions with the targets after being <br />
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<br />
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labeled with rhenium (Re) and technetium (Tc) were studied by in silico. The <br />
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<br />
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interactions of porphyrin derivatives with protein target of cancer such as spleen <br />
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tyrosin kinase, epidermal growth factor receptor, carbonic anhydrase IX (CAIX), <br />
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<br />
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and REV-ERBβwere then analyzed after performing molecular docking with <br />
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<br />
<br />
AutoDock 4.2 and molecular dynamic simulation with Gromacs2016. The <br />
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<br />
<br />
simulations showed that studied porphyrins have affinity to the targets and the <br />
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<br />
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interactions were dominated by hydrophobic interactions. Re- and Tc-porphyrin <br />
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<br />
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also have affinity to the targets although the porphyrins have been already labeled. <br />
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For each protein target, the porphyrin with best affinity was determined and the <br />
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<br />
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free binding energy between the best porphyrin-target complex was also calculated <br />
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<br />
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by MM/PBSA method. The toxicity of all porphyrins were also predicted by using <br />
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<br />
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ADMET Predictor v 8.1. In general, it was predicted that porphyrin derivatives are <br />
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cardiotoxic, hepatotoxic, and toxic to reproduction system, however, they are not <br />
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mutagenic, and their carcinogenicity level were not high. All porphyrin derivatives <br />
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<br />
<br />
were successfully synthesized by Adler method, and they were characterized by <br />
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UV/Vis, <br />
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1 <br />
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H-NMR, <br />
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13 <br />
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C-NMR, and LRMS MALDI-TOF. The reaction pathway in this <br />
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Adler method was also studied by in silico study and it was known that the keystep <br />
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<br />
of the reaction is the first step when the aldehyde reacts with pyrrole based on the <br />
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<br />
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reactivity of the aldehyde. The cytotoxicity activities of all porphyrin derivatives <br />
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<br />
<br />
were tested by MTT assay against cancer cell (HeLa, WIDR, MCF-7, T47D, and <br />
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HepG2 cell lines) and normal cell (Vero cell line). The in vitro test results showed <br />
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iv <br />
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that all studied porphyrins have good affinity against cancer cell, having higher <br />
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affinity to the cancer cell than to that of the normal cell, and they are categorized <br />
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as marginally active compound with the IC50 < 5 mM. Based on these results, it can <br />
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<br />
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be concluded that all studied porphyrins were potential as an anticancer agents, <br />
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and porphyrins bearing bis(3,4-ethylcarboxymethylenoxy) phenyl (BECP) as mesosubstituent have better potential as a radiopharmaceutical ligand kit after the ester <br />
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groups of BECP were hydrolyzed. <br />
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