The Lactone Form of Stachybotrydial: A New Inhibitor of Dihydrofolate Reductase from <i>Stachybotrys</i> sp. FN298

Abstract

Dihydrofolate reductase (DHFR) has been confirmed to be a novel target for antibacterial drug development. In this study, we determined that a fungal metabolite from Stachybotrys sp. FN298 can inhibit the DHFR of Staphylococcus aureus. Its structure was identified as a lactone form of stachybotrydial using mass spectrometry and nuclear magnetic resonance analysis. This compound inhibited S. aureus DHFR with a half-maximal inhibitory concentration of 41 µM. It also prevented the growth of S. aureus and methicillinresistant S. aureus (MRSA) with a minimum inhibitory concentration of 32 µg·mL 1 . To our knowledge, this is the first description of a DHFR inhibitor of microbial origin. The inhibitory function of the lactone form of stachybotrydial highlights its potential for development into a new broad-spectrum antibacterial agent and as an agent against MRSA.

Stachybotrysin, an Osteoclast Differentiation Inhibitor from the Marine-Derived Fungus Stachybotrys sp. KCB13F013

“…The HMBC correlations of H 2 -7′ to C-4′ (δ C 149.6), C-5′ (δ C 97.9), and C-8′ (δ C 167.9) indicated the presence of a lactone moiety that was connected to the phenylspirodrimane by the HMBC correlations of H 2 -7′ to C-3′ (δ C 100.8), C-4′ (δ C 149.6), and C-5′ (δ C 97.9). Interestingly, the molecular formula of 2 was the same as that of stachybotrylactone. , The lactone carbonyl of stachybotrylactone was located at C-7′ rather than C-8′ through the HMBC correlations of H-3′ to the carbonyl at C-7′ and lactone methylene protons to C-6′ . On the other hand, the lactone carbonyl of 2 was located at C-8′.…”

“…Interestingly, the molecular formula of 2 was the same as that of stachybotrylactone. 22,23 The lactone carbonyl of stachybotrylactone was located at C-7′ rather than C-8′ through the HMBC correlations of H-3′ to the carbonyl at C-7′ and lactone methylene protons to C-6′. 22 On the other hand, the lactone carbonyl of 2 was located at C-8′.…”

Seven new cytotoxic phenylspirodrimane derivatives from the endophytic fungus Stachybotrys chartarum

“…Meanwhile, the spirobenzofuran moiety was revealed through correlations from H 2 -11 to C-1 0 , C-2 0 , C-6 0 , C-9, and C-10. It was further noticed that the carbonyl C-7 0 and the oxygenated methylene C-8 0 seen in stachybotrylactones 20 were replaced by the hemiacetal C-8 0 at d H 5.70/d C 97.3 and the oxygenated methine C-7 0 at d H 4.72/d C 64.1 in 1. The methine nature of C-7 0 revealed the C-7 0 -C-7 000 bond between the two symmetrical units.…”

“…The molecular formula of stachybochartin A (1) was determined as C 46 H 62 O 10 , from the positive HRESIMS ion peak at m/z: 797.4232 [ The above data resembled that from stachybotrylactones, yet only showed half the total mass revealed by MS studies. 20 Therefore, 1 was deduced to be a dimeric phenylspirodrimane with a symmetrical structure. HMBC results further conrmed the phenylspirodrimane structure (Fig.…”

Unveiling the Efficacy of Sesquiterpenes from Marine Sponge Dactylospongia elegans in Inhibiting Dihydrofolate Reductase Using Docking and Molecular Dynamic Studies

“…FN298. It demonstrated S. aureus`s DHFR (IC 50 , 41 µM) inhibition potential and prohibited MRSA growth ( MIC, 32 µg/mL), suggesting its possible efficacy as an antibacterial agent versus MRSA [ 26 ]. Coscinoquinol purified from the Australian Coscinoderma sp.…”