TY - JOUR
T1 - In-silico, synthesis, structure elucidation and anticancer activity study of 2-(3,4-dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one
AU - Kesuma, Dini
AU - Yuniarta, Tegar Achsendo
AU - Putra, Galih Satrio
AU - Sumari, Sumari
AU - Sulistyowaty, Melanny Ika
AU - Anwari, Farida
N1 - Funding Information:
The authors are thankful to ITD Airlangga for collecting all spectra data especially 1D and 2D NMR and Hiroshima University (Katsuyoshi Matsunami) for the help in MS data acquisition
Publisher Copyright:
© 2022 Pakistan Journal of Pharmaceutical Sciences. All rights reserved.
PY - 2022/9
Y1 - 2022/9
N2 - The research aims to synthesize 2-(3,4-dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one and evaluate its anticancer activity against MCF-7. This compound was selected based on in-silico study conducted against several dihalophenylbenzoxazinone analogues using molecular docking towards Methionyl-tRNA synthetase. Synthesis of target compound was carried out using anthranilic acid and 3,4-dichlorobenzoyl chloride. The resulting compound was characterized using various spectroscopic analysis: 1D and 2D NMR, infrared and MS. In-silico studies was performed by MVD. Several designed compounds were docked into the active site on Methionyl-tRNA Synthetase (1PG2). Anticancer activity was evaluated by MTT Assay against MCF-7. 2-(3,4-dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one has been successfully synthesized with decent amount of yield 88 %. Its spectroscopic analysis 1D and 2D NMR, MS, FTIR has proven the chemical structure of compound. In-silico studies toward the enzyme showed docking score of - 76.04 Kcal/mol, higher than its native ligand (-93.50 Kcal/mol). Meanwhile, MTT assay result against MCF-7 showed IC50 value of 68.59ppm. Based on preliminary in-silico studies inhibited Methionyl-tRNA Synthetase, 2-(3,4-dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one was synthesized and tested in-vitro against MCF-7. Albeit the compound does not possess better docking score than native ligand, it is still argued that benzoxazine ring can be considered as a potential anticancer agent, as showed by MTT assay result which indicated moderate cytotoxicity.
AB - The research aims to synthesize 2-(3,4-dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one and evaluate its anticancer activity against MCF-7. This compound was selected based on in-silico study conducted against several dihalophenylbenzoxazinone analogues using molecular docking towards Methionyl-tRNA synthetase. Synthesis of target compound was carried out using anthranilic acid and 3,4-dichlorobenzoyl chloride. The resulting compound was characterized using various spectroscopic analysis: 1D and 2D NMR, infrared and MS. In-silico studies was performed by MVD. Several designed compounds were docked into the active site on Methionyl-tRNA Synthetase (1PG2). Anticancer activity was evaluated by MTT Assay against MCF-7. 2-(3,4-dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one has been successfully synthesized with decent amount of yield 88 %. Its spectroscopic analysis 1D and 2D NMR, MS, FTIR has proven the chemical structure of compound. In-silico studies toward the enzyme showed docking score of - 76.04 Kcal/mol, higher than its native ligand (-93.50 Kcal/mol). Meanwhile, MTT assay result against MCF-7 showed IC50 value of 68.59ppm. Based on preliminary in-silico studies inhibited Methionyl-tRNA Synthetase, 2-(3,4-dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one was synthesized and tested in-vitro against MCF-7. Albeit the compound does not possess better docking score than native ligand, it is still argued that benzoxazine ring can be considered as a potential anticancer agent, as showed by MTT assay result which indicated moderate cytotoxicity.
KW - Anticancer
KW - MTT assay
KW - benzoxazinone
KW - elucidation
KW - molecular docking
UR - http://www.scopus.com/inward/record.url?scp=85140622570&partnerID=8YFLogxK
U2 - 10.36721/PJPS.2022.35.5.REG.1391-1398.1
DO - 10.36721/PJPS.2022.35.5.REG.1391-1398.1
M3 - Article
AN - SCOPUS:85140622570
SN - 1011-601X
VL - 35
SP - 1391
EP - 1398
JO - Pakistan Journal of Pharmaceutical Sciences
JF - Pakistan Journal of Pharmaceutical Sciences
IS - 5
ER -