New Production of Antibacterial Polycyclic Quinazoline Alkaloid, Thielaviazoline, from Anthranilic Acid by the Marine-Mudflat-Derived Fungus Thielavia sp.

Alain Simplice Leutou; Keumja Yun; Byeng Wha Son

doi:10.20307/nps.2016.22.3.216

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Leutou, Yun, and Son: New Production of Antibacterial Polycyclic Quinazoline Alkaloid, Thielaviazoline, from Anthranilic Acid by the Marine-Mudflat-Derived Fungus Thielavia sp.

Original Article

Natural Product Sciences 2016;22(3):216-219.

Published online: 17 January 2016

DOI: https://doi.org/10.20307/nps.2016.22.3.216

New Production of Antibacterial Polycyclic Quinazoline Alkaloid, Thielaviazoline, from Anthranilic Acid by the Marine-Mudflat-Derived Fungus Thielavia sp.

Alain Simplice Leutou, Keumja Yun, Byeng Wha Son^∗

Department of Chemistry, Pukyong National University, Busan 608-737, Korea

^∗Author for correspondence Byeng Wha Son, Department of Chemistry, Pukyong National University, Busan 608-737, Korea Tel: +82-51-629-5592; E-mail: sonbw@pknu.ac.kr

Received 7 March 2016 Revised 8 April 2016 Accepted 11 April 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The microbial transformation of anthranilic acid (1) by the marine-mudflat-derived fungus Thielavia sp. produced an antibacterial polycyclic quinazoline alkaloid, thielaviazoline (2). The stereostructure of the metabolite was assigned based on detailed spectroscopic data analyses including comparison of the NMR (¹H and¹³C) data with those of reported compound (2). Compound 2 displayed in vitro antimicrobial activity against methicillin-resistant and multidrug-resistant Staphylococcus aureus (MRSA and MDRSA), with minimum inhibitory concentrations (MICs) of 6.25 and 12.5 µ g/mL, respectively. Compound 2 also showed potent radical-scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) with an IC₅₀ of 11 µM, which was more active than the positive control, L-ascorbic acid (IC₅₀, 20.0 µM).

Keywords: Thielaviazoline, Polycyclic quinazoline alkaloid, Thielavia sp., Microbial transformation

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Fig. 1.

Microbial synthesis of thielaviazoline (2) from anthranilicacid (1) by the marine-mudflat-derived fungus Thielavia sp.

Fig. 2.

EI-MS fragmentation for thielaviazoline (2).

Table 1.

NMR spectra data for thielaviazoline (2)^a

thielaviazoline(2)
Position	δ_H (mult, J)	δ_C (mult)	HMBC (H to C)
1	5.09 (s)	693.1 (d)	C-2, -3, -7, -9, -11, 1-OMe
2		126.7 (s)
3	7.23 (m)^b	129.7 (d)	C-1, -2, -5, -7
4	7.02 (m)^c	123.7 (d)^α	C-2, -6
5	7.21 (m)^b	123.5 (d)	C-3, -7
6	7.14 (m)^d	128.0 (d)	C-2, -4
7		144.9 (s)
8-N
9	5.23 (s)	662.7 (d)	C-1, -7, -11, -17, -19, -20, -21
10-N
11		142.3 (s)
12	7.03 (m)^c	128.5 (d)^β	C-14, -16
13	7.09 (m)	128.4 (d)^β
14	7.02 (m)^c	123.8 (d)^α
15	7.12 (m)^d	128.8 (d)^γ	C-11, -13, -17
16		130.0 (s)
17	5.36 (d,4.3)	668.3 (d)	C-7, -9, -11, -19
18-NH	7.05 (m)^c		C-16, -17, -19, -20, -24
19		142.0 (s)
2021	7.25 (m)^b	120.6 (s)128.9 (d)^γ	C-9, -19, -23
22	6.69 (dd,7.5, 7.3)	121.2 (d)
23	6.94 (dd,7.5, 7.3)	123.9 (d)
24	6.64 (d,8.0)	115.6 (d)	C-19, -20, -22
1-OMe	3.82 (s)	654.9 (q)	C-1

^a Recorded in DMSO-d₆ at 400 MHz (¹H) and 100 MHz (¹³C).

b∼d and α∼γ Exchangeable, respectively.

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