Anticancer and antimicrobial compounds from Xylia xylocarpa and Coscinium fenestratum and structure-activity relationship studies

Abstract

Sandaracopimaradiene-3β,18-diol (D1), sandaracopimaradien-3-one (D2) sandaracopimaradien-3β-ol (D3) and sandaracopimaric acid (D4) were isolated from the dichloromethane extract of the heartwoods of Xylia xylocarpa (Roxb.) Taub. D1 was selected as a model for SAR study. Five derivatives: D7, D8, D15, D18 and D19 were synthesized and displayed moderate to good antibacterial activity against Staphylococcus aureus, Propionibacterium acnes, Streptococcus mutans, Streptococcus sobrinus, and Salmonella typhi. D7 and D19 revealed the best MIC as 31.2–62.5 μM to inhibit S. aureus, S. mutans, S. sobrinus, and S. typhi. Only D7 showed MBC at 62.5 μM to kill S. sobrinus. C2 was synthesized via cyclopropanation of D1 with alkynyl diazoacetate L3. The cytotoxicity of D1-D3 and their derivatives (D7, D8, D15, D18, D19 and C2) against HepG2 (liver hepatocellular carcinoma) by MTS assay displayed that D7, D15 and D18 expressed good activity with IC50 3.45±0.47, 1.00±0.47 and 0.99±0.08 μM, respectively.

Berberine chloride (B1), isolated from the vines of Coscinium fenestratum (Goetgh.) Colebr., was used as a lead structure to synthesize eight derivatives B2-B9 for SAR study. Only B3 exhibited the highest antibacterial activity against Xanthomonas oryzae pv. oryzae and pv. oryzicola. B9, B8, and B7 showed good antioxidant activity (IC50 = 10.72 ± 1.76, 55.24 ± 2.24, and 87.35 ± 6.65 μM, respectively) via DPPH assay. For cytotoxicity assay against human fibrosarcoma cells (HT1080) using MTT regent, the sequence of IC50 at 7-day treatment stated that B1 < B9 < B7 (0.44 ± 0.03, 2.88 ± 0.23, and 6.05 ± 0.64 μM, respectively). B7 and B9 showed approximately the same level of CAT expression and significantly up-regulation of SOD expression in a dose-dependent manner compared to B1 treatment for 7-day exposure using reverse transcription-polymerase chain reaction (RT-PCR) assay. These findings displayed better direct-antioxidant activity of the derivatives containing phenolic groups (B7-B9) than B1 in a cell-free system. For cell-based system, B1 was able to express better cytotoxic activity than its derivatives (B7-B9), whereas B7 and B9 showed better up-regulation of SOD gene expression.