In Silico Study, Synthesis, and Cytotoxic Activities of Porphyrin Derivatives

Fransiska Kurniawan; Youhei Miura; Rahmana Emran Kartasasmita; Naoki Yoshioka; Abdul Mutalib; Daryono Hadi Tjahjono

doi:10.3390/ph11010008

In Silico Study, Synthesis, and Cytotoxic Activities of Porphyrin Derivatives

Pharmaceuticals (Basel). 2018 Jan 20;11(1):8. doi: 10.3390/ph11010008.

Authors

Fransiska Kurniawan¹, Youhei Miura², Rahmana Emran Kartasasmita³, Naoki Yoshioka⁴, Abdul Mutalib⁵, Daryono Hadi Tjahjono⁶

Affiliations

¹ School of Pharmacy, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132, Indonesia. fransiskakurniawan@yahoo.com.
² Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan. y-miura@applc.keio.ac.jp.
³ School of Pharmacy, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132, Indonesia. kartasasmita@fa.itb.ac.id.
⁴ Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan. yoshioka@applc.keio.ac.jp.
⁵ Center for Radioisotope and Radiopharmaceutical Technology, National Nuclear Energy Agency (BATAN), Serpong, Tangerang 15310, Indonesia. mutalib@batan.go.id.
⁶ School of Pharmacy, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132, Indonesia. daryonohadi@fa.itb.ac.id.

Abstract

Five known porphyrins, 5,10,15,20-tetrakis(p-tolyl)porphyrin (TTP), 5,10,15,20-tetrakis(p-bromophenyl)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(p-aminophenyl)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 DBECPDPzP-REV-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.

Keywords: cancer cell lines; cytotoxicity; molecular dynamics; porphyrin derivative; synthesis.