TY - JOUR
T1 - In silico study, synthesis, and cytotoxic activities of porphyrin derivatives
AU - Kurniawan, Fransiska
AU - Miura, Youhei
AU - Kartasasmita, Rahmana Emran
AU - Mutalib, Abdul
AU - Yoshioka, Naoki
AU - Tjahjono, Daryono Hadi
N1 - Funding Information:
Acknowledgments: FK wishes to thank PMDSU and PKPI Scholarship 2016 from the Ministry of Research, Technology, and Higher Education (MRTHE), the Republic of Indonesia. This research was financially supported by Hibah PMDSU 2016 and Riset Unggulan Perguruan Tinggi 2016 and 2017 from MRTHE (D.H.T).
Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/3
Y1 - 2018/3
N2 - Five known porphyrins, 5,10,15,20-tetrakis(p-tolyl)porphyrin (TTP), 5,10,15,20-tetrakis(pbromophenyl) porphyrin (TBrPP), 5,10,15,20-tetrakis(p-aminophenyl)porphyrin (TAPP), 5,10,15- tris(tolyl)-20-mono(p-nitrophenyl)porphyrin (TrTMNP), 5,10,15-tris(tolyl)-20-mono(paminophenyl) porphyrin (TrTMAP), and three novel porphyrin derivatives, 5,15-di-[bis(3,4- ethylcarboxymethylenoxy)phenyl]-10,20-di(p-tolyl)porphyrin (DBECPDTP), 5,10-di-[bis(3,4- ethylcarboxymethylenoxy)phenyl]-15,20-di-(methylpyrazole-4-yl)porphyrin (cDBECPDPzP), 5,15-di- [bis(3,4-ethylcarboxymethylenoxy)phenyl]-10,20-di-(methylpyrazole-4-yl)porphyrin (DBECPDPzP), were used to study their interaction with protein targets (in silico study), and were synthesized. Their cytotoxic activities against cancer cell lines were tested using 3-(4,5-dimetiltiazol-2-il)-2,5- difeniltetrazolium bromide (MTT) assay. The interaction of porphyrin derivatives with carbonic anhydrase IX (CAIX) and REV-ERBβ proteins were studied by molecular docking and molecular dynamic simulation. In silico study results reveal that DBECPDPzP and TrTMNP showed the highest binding interaction with REV- ERBβ and CAIX, respectively, and both complexes of DBECPDPzPREV- ERBβ and TrTMNP-CAIX showed good and comparable stability during molecular dynamic simulation. The studied porphyrins have selective growth inhibition activities against tested cancer cells and are categorized as marginally active compounds based on their IC50.
AB - Five known porphyrins, 5,10,15,20-tetrakis(p-tolyl)porphyrin (TTP), 5,10,15,20-tetrakis(pbromophenyl) porphyrin (TBrPP), 5,10,15,20-tetrakis(p-aminophenyl)porphyrin (TAPP), 5,10,15- tris(tolyl)-20-mono(p-nitrophenyl)porphyrin (TrTMNP), 5,10,15-tris(tolyl)-20-mono(paminophenyl) porphyrin (TrTMAP), and three novel porphyrin derivatives, 5,15-di-[bis(3,4- ethylcarboxymethylenoxy)phenyl]-10,20-di(p-tolyl)porphyrin (DBECPDTP), 5,10-di-[bis(3,4- ethylcarboxymethylenoxy)phenyl]-15,20-di-(methylpyrazole-4-yl)porphyrin (cDBECPDPzP), 5,15-di- [bis(3,4-ethylcarboxymethylenoxy)phenyl]-10,20-di-(methylpyrazole-4-yl)porphyrin (DBECPDPzP), were used to study their interaction with protein targets (in silico study), and were synthesized. Their cytotoxic activities against cancer cell lines were tested using 3-(4,5-dimetiltiazol-2-il)-2,5- difeniltetrazolium bromide (MTT) assay. The interaction of porphyrin derivatives with carbonic anhydrase IX (CAIX) and REV-ERBβ proteins were studied by molecular docking and molecular dynamic simulation. In silico study results reveal that DBECPDPzP and TrTMNP showed the highest binding interaction with REV- ERBβ and CAIX, respectively, and both complexes of DBECPDPzPREV- ERBβ and TrTMNP-CAIX showed good and comparable stability during molecular dynamic simulation. The studied porphyrins have selective growth inhibition activities against tested cancer cells and are categorized as marginally active compounds based on their IC50.
KW - Cancer cell lines
KW - Cytotoxicity
KW - Molecular dynamics
KW - Porphyrin derivative
KW - Synthesis
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U2 - 10.3390/ph11010008
DO - 10.3390/ph11010008
M3 - Article
AN - SCOPUS:85041993661
SN - 1424-8247
VL - 11
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 1
M1 - 8
ER -
