Preparation and Cytotoxic Evaluation of PGV-1 Derivative, CCA-1.1, as a New Curcumin Analog with Improved-Physicochemical and Pharmacological Properties

Rohmad Yudi Utomo; Febri Wulandari; Dhania Novitasari; Beni Lestari; Ratna Asmah Susidarti; Riris Istighfari Jenie; Jun-Ya Kato; Sardjiman Sardjiman; Edy Meiyanto

doi:10.34172/apb.2022.063

Preparation and Cytotoxic Evaluation of PGV-1 Derivative, CCA-1.1, as a New Curcumin Analog with Improved-Physicochemical and Pharmacological Properties

Adv Pharm Bull. 2022 May;12(3):603-612. doi: 10.34172/apb.2022.063. Epub 2021 Jul 4.

Authors

Rohmad Yudi Utomo^{1

2}, Febri Wulandari¹, Dhania Novitasari¹, Beni Lestari¹, Ratna Asmah Susidarti^{1

2}, Riris Istighfari Jenie^{1

3}, Jun-Ya Kato⁴, Sardjiman Sardjiman², Edy Meiyanto^{1

3}

Affiliations

¹ Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada (UGM), Sekip Utara, Yogyakarta 55281, Indonesia.
² Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, UGM, Sekip Utara, Yogyakarta 55281, Indonesia.
³ Macromolecular Engineering Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy UGM, Sekip Utara, Yogyakarta 55281, Indonesia.
⁴ Laboratory of Tumor Cell Biology, Division of Bioligical Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, 630-0192, Japan.

Abstract

Purpose: This study aimed to challenge the anticancer potency of pentagamavunone-1 (PGV- 1) and obtain a new compound (Chemoprevention-Curcumin Analog 1.1, CCA-1.1) with improved chemical and pharmacological properties. Methods: CCA-1.1 was prepared by changing the ketone group of PGV-1 into a hydroxyl group with NaBH₄ as the reducing agent. The product was purified under preparative layer chromatography and confirmed with HPLC to show about 93% purity. It was tested for its solubility, stability, and cytotoxic activities on several cancer cells. The structure of the product was characterized using ¹HNMR, ¹³C-NMR, FT-IR, and HR-mass spectroscopy. Results: Molecular docking analysis showed that CCA-1.1 performed similar or better interaction to NF-κB pathway-related signaling proteins (HER2, EGFR, IKK, ER-alpha, and ER-beta) and reactive oxygen species (ROS) metabolic enzymes (NQO1, NQO2, GSTP1, AKC1R1, and GLO1) compared with PGV-1, indicating that CCA-1.1 exhibits the same or better anticancer activity than PGV-1. CCA-1.1 also showed better solubility and stability than PGV-1 in aqueous solution at pH 1.0-7.4 under light exposure at room temperature. The cytotoxic activities of CCA-1.1 against several (10) cancer cell lines revealed the same or better potency than PGV-1. Conclusion: In conclusion, CCA-1.1 performs better chemical and anticancer properties than PGV-1 and shows promise as an anticancer agent with high selectivity.

Keywords: CCA-1.1; Curcumin analog; Cytotoxic; NF-κB; Reactive oxygen species.