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Three novel ent -kaurane diterpenes, namely sigesbeckin A-C ( 1 - 3 ), in conjunction with eight previously identified analogues ( 4 - 11 ), were isolated from Sigesbeckia orientalis . Their chemical structures were resolved through multiple spectroscopic analyses. All compounds were assessed for antimicrobial bioactivity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. In particular, compounds 1 and 5 demonstrated moderate efficacy, with MIC values of 64 μg/mL. Moreover, compounds 3 , 5 , and 11 were found to synergize with doxorubicin hydrochloride (DOX) and vancomycin (VAN) against MRSA and VRE. The aforementioned findings offer valuable insights for the development of novel alternatives to antibiotics, which can effectively tackle the escalating issue of antibiotic resistance.

Four new germacrane sesquiterpene dilactones, 2 β -hydroxyl-11 β ,13-dihydrodeoxymikanolide ( 1 ), 3 β -hydroxyl-11 β ,13-dihydrodeoxymikanolide ( 2 ), 1 α ,3 β -dihydroxy-4,9-germacradiene-12,8:15,6-diolide ( 3 ), and (11 β ,13-dihydrodeoxymikanolide-13-yl)-adenine ( 4 ), together with five known ones ( 5 - 9 ) were isolated from the aerial parts of Mikania micrantha . Their structures were elucidated on the basis of extensive spectroscopic analysis. Compound 4 is featured with an adenine moiety in the molecule, which is the first nitrogen-containing sesquiterpenoid so far isolated from this plant species. These compounds were evaluated for their in vitro antibacterial activity against four Gram-(+) bacteria of Staphyloccocus aureus ( SA ), methicillin-resistant Staphylococcus aureus ( MRSA ), Bacillus cereus ( BC ) and Curtobacterium. flaccumfaciens ( CF ), and three Gram-(-) bacteria of Escherichia coli ( EC ), Salmonella. typhimurium ( SA ), and Pseudomonas Solanacearum ( PS ). Compounds 4 and 7 - 9 were found to show strong in vitro antibacterial activity toward all the tested bacteria with the MIC values ranging from 1.56 to 12.5 µg/mL. Notably, compounds 4 and 9 showed significant antibacterial activity against the drug-resistant bacterium of MRSA with MIC value 6.25 µg/mL, which was close to reference compound vancomycin (MIC 3.125 µg/mL). Compounds 4 and 7 - 9 were further revealed to show in vitro cytotoxic activity toward human tumor A549, HepG2, MCF-7, and HeLa cell lines, with IC 50 values ranging from 8.97 to 27.39 μM. No antibacterial and cytotoxic activity were displayed for the other compounds. The present research provided new data to support that M. micrantha is rich in structurally diverse bioactive compounds worthy of further development for pharmaceutical applications and for crop protection in agricultural fields.

Three new polycyclic phenol derivatives, 2-acetyl-4-hydroxy-6H-furo [2,3-g]chromen-6-one ( 1 ), 2-(1',2'-dihydroxypropan-2'-yl)-4-hydroxy-6H-furo [2,3-g][1]benzopyran-6-one ( 2 ) and 3,8,10-trihydroxy-4,9-dimethoxy-6H-benzo[c]chromen-6-one ( 8 ), along with seven known ones ( 3 - 7 , 9 and 10 ) were isolated for the first time from the leaves of Spermacoce latifolia . Their structures were determined by spectroscopic analysis and comparison with literature-reported data. These compounds were tested for their in vitro antibacterial activity against four Gram-(+) bacteria: Staphyloccocus aureus ( SA ), methicillin-resistant Staphylococcus aureus ( MRSA ), Bacillus cereus ( BC ), Bacillus subtilis ( BS ), and the Gram-(-) bacterium Escherichia coli . Compounds 1 , 2 , 5 and 8 showed antibacterial activity toward SA , BC and BS with MIC values ranging from 7.8 to 62.5 µg/mL, but they were inactive to MRSA . Compound 4 not only showed the best antibacterial activity against SA , BC and BS , but it further displayed significant antibacterial activity against MRSA (MIC 1.95 µg/mL) even stronger than vancomycin (MIC 3.9 µg/mL). No compounds showed inhibitory activity toward E. coli . Further bioassay indicated that compounds 1 , 4 , 5 , 6 , 8 and 9 showed in vitro α -glucosidase inhibitory activity, among which compound 9 displayed the best α -glucosidase inhibitory activity with IC 50 value (0.026 mM) about 15-fold stronger than the reference compound acarbose (IC 50 0.408 mM). These results suggested that compounds 4 , 8 and 9 were potentially highly valuable compounds worthy of consideration to be further developed as an effective anti- MRSA agent or effective α -glucosidase inhibitors, respectively. In addition, the obtained data also supported that S. latifolia was rich in structurally diverse bioactive compounds worthy of further investigation, at least in searching for potential antibiotics and α -glucosidase inhibitors.

Bacterial infections are regarded as one of the leading causes of fatal morbidity and death in patients infected with diseases. The ability of microorganisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), to develop resistance to current drugs has evoked the need for a continuous search for new drugs with better efficacies. Hence, a series of non-PAINS associated pyrrolylated-chalcones ( 1 - 15 ) were synthesized and evaluated for their potency against MRSA. The hydroxyl-containing compounds ( 8 , 9 , and 10 ) showed the most significant anti-MRSA efficiency, with the MIC and MBC values ranging from 0.08 to 0.70 mg/mL and 0.16 to 1.88 mg/mL, respectively. The time-kill curve and SEM analyses exhibited bacterial cell death within four hours after exposure to 9 , suggesting its bactericidal properties. Furthermore, the docking simulation between 9 and penicillin-binding protein 2a (PBP2a, PDB ID: 6Q9N) suggests a relatively similar bonding interaction to the standard drug with a binding affinity score of -7.0 kcal/mol. Moreover, the zebrafish model showed no toxic effects in the normal embryonic development, blood vessel formation, and apoptosis when exposed to up to 40 µM of compound 9 . The overall results suggest that the pyrrolylated-chalcones may be considered as a potential inhibitor in the design of new anti-MRSA agents., Competing Interests: The authors declare no conflict of interest.

Ruta chalepensis L. (Rutaceae), a perennial herb with wild and cultivated habitats, is well known for its traditional uses as an anti-inflammatory, analgesic, antipyretic agent, and in the treatment of rheumatism, nerve diseases, neuralgia, dropsy, convulsions and mental disorders. The antimicrobial activities of the crude extracts from the fruits, leaves, stem and roots of R. chalepensis were initially evaluated against two Gram-positive and two Gram-negative bacterial strains and a strain of the fungus Candida albicans . Phytochemical investigation afforded 19 compounds, including alkaloids, coumarins, flavonoid glycosides, a cinnamic acid derivative and a long-chain alkane. These compounds were tested against a panel of methicillin-resistant Staphylococcus aureus (MRSA) strains, i.e., ATCC 25923, SA-1199B, XU212, MRSA-274819 and EMRSA-15. The MIC values of the active compounds, chalepin ( 9 ), chalepensin ( 10 ), rutamarin ( 11 ), rutin 3'-methyl ether ( 14 ), rutin 7,4'-dimethyl ether ( 15 ), 6-hydroxy-rutin 3',7-dimethyl ether ( 16 ) and arborinine ( 18 ) were in the range of 32-128 µg/mL against the tested MRSA strains. Compounds 10 and 16 were the most active compounds from R. chalepensis , and were active against four out of six tested MRSA strains, and in silico studies were performed on these compounds. The anti-MRSA activity of compound 16 was comparable to that of the positive control norfloxacin (MICs 32 vs 16 μg/mL, respectively) against the MRSA strain XU212, which is a Kuwaiti hospital isolate that possesses the TetK tetracycline efflux pump. This is the first report on the anti-MRSA property of compounds isolated from R. chalepensis and relevant in silico studies on the most active compounds.

There is an urgent need to search for new antibiotics to counter the growing number of antibiotic-resistant bacterial strains, one of which is methicillin-resistant Staphylococcus aureus (MRSA). Herein, we report a Streptomyces sp. strain MUSC 125 from mangrove soil in Malaysia which was identified using 16S rRNA phylogenetic and phenotypic analysis. The methanolic extract of strain MUSC 125 showed anti-MRSA, anti-biofilm and antioxidant activities. Strain MUSC 125 was further screened for the presence of secondary metabolite biosynthetic genes. Our results indicated that both polyketide synthase ( pks ) gene clusters, pks I and pks II, were detected in strain MUSC 125 by PCR amplification. In addition, gas chromatography-mass spectroscopy (GC-MS) detected the presence of different chemicals in the methanolic extract. Based on the GC-MS analysis, eight known compounds were detected suggesting their contribution towards the anti-MRSA and anti-biofilm activities observed. Overall, the study bolsters the potential of strain MUSC 125 as a promising source of anti-MRSA and antibiofilm compounds and warrants further investigation.

Twenty-five new derivatives of 8-hydroxycycloberberine ( 1 ) were synthesized and evaluated for their activities against Gram-positive bacteria, taking 1 as the lead. Part of them displayed satisfactory antibacterial activities against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), as well as vancomycin-intermediate Staphylococcus aureus (VISA). Especially, compound 15a displayed an excellent anti-MRSA activity with MICs (minimum inhibitory concentrations) of 0.25⁻0.5 μg/mL, better than that of 1 . It also displayed high stability in liver microsomes and whole blood, and the LD 50 value of over 65.6 mg·kg -1 in mice via intravenous route, suggesting a good druglike feature. The mode of action showed that 15a could effectively suppress topo IV-mediated decatenation activity at the concentration of 7.5 μg/mL, through binding a different active pocket of bacterial topo IV from quinolones. Taken together, the derivatives of 1 constituted a promising kind of anti-MRSA agents with a unique chemical scaffold and a specific biological mechanism, and compound 15a has been chosen for the next investigation.