Maculosin, a non-toxic antioxidant compound isolated from Streptomyces sp. KTM18

Abstract

Context

Streptomyces species are prolific sources of bioactive secondary metabolites known especially for their antimicrobial and anticancer activities.

Objective

This study sought to isolate and characterize antioxidant molecules biosynthesized by Streptomyces sp. KTM18. The antioxidant potential of an isolated compound and its toxicity were accessed.

Materials and methods

The compound was purified using bioassay-guided chromatography techniques. Nuclear magnetic resonance (NMR) experiments were carried out for structure elucidation. The antioxidant potential of the isolated compound was determined using DPPH free radical scavenging assay. The toxicity of the isolated compound was measured using a brine shrimp lethality (BSL) assay.

Results

Ethyl acetate extract of Streptomyces sp. KTM18 showed more than 90% inhibition of DPPH free radical at 50 µg/mL of the test concentration. These data were the strongest among 13 Streptomyces isolates (KTM12–KTM24). The active molecule was isolated and characterized as maculosin (molecular formula, C₁₄H₁₆N₂O₃ as determined by the [M + H]⁺ peak at 261.1259). The DPPH free radical scavenging activity of pure maculosin was higher (IC₅₀, 2.16 ± 0.05 µg/mL) than that of commercial butylated hydroxyanisole (BHA) (IC₅₀, 4.8 ± 0.05 µg/mL). No toxicity was observed for maculosin (LD₅₀, <128 µg/mL) in brine shrimp lethality assay (BSLA) up to the compound’s antioxidant activity (IC₅₀) concentration range. The commercial standard, berberine chloride, showed toxicity in BSLA with an LD₅₀ value of 8.63 ± 0.15 µg/mL.

Conclusions

Maculosin may be a leading drug candidate in various cosmetic and therapeutic applications owing to its strong antioxidant and non-toxic properties.

Keywords:

• Bioactivity
• brine shrimp toxicity
• chromatography
• diketopiperazine
• DPPH free radical
• natural products

Acknowledgements

The authors are grateful to Esa Gurung, Jyoti Basnet, Aarzu Thapa and Sagar Atri from Kantipur Valley College for their cooperation in fieldwork and laboratory support. HDB, NA and SA are thankful to Prof. Harald Gross, Tuebingen University, for providing laboratory facilities including HPLC, HR-ESIMS and NMR.

Disclosure statement

The authors have no conflicts of interest to declare.

Additional information

Funding

Authors RM, HDB and BP are thankful to the University Grant Commission, Nepal, for the financial support in the form of a collaborative research grant. HDB is indebted to the AvH Foundation for providing a short research stay fellowship to complete this work.