Anti-MRSA agent 4 (compound 7a), a selective and potent inhibitor of Gram-positive Methicillin-resistant Staphylococcus aureus (MRSA) growth, demonstrates a minimum inhibitory concentration (MIC) of ≤ 0.26 µM. It exhibits neither cytotoxic nor hemolytic activity in HEK293 cells [1].

Anti-MRSA agent 7 (Compound 12) serves as a potent antibacterial compound effectively inhibiting both S. aureus and E. coli DNA gyrases, as well as topo IV enzymes from the same organisms, with IC50 values of 0.185 μM, 0.365 μM, 0.341 μM, and 0.059 μM, respectively [1].

Anti-MRSA agent 2 (compound 14) is a good inhibitor of methicillin-resistant Staphylococcus aureus (MRSA) (MIC: 0.098 μg/ml) with relatively low toxicity to normal cells. anti-MRSA agent 2 is a strong disruptor of bacterial membranes and has a good ability to bind to bacterial genomic DNA.

Anti-MRSA agent 3 inhibits methicillin-resistant Staphylococcus aureus (MRSA) activity significantly (MIC: 0.098 μg/ml) with low toxicity to normal cells. anti-MRSA agent 3 has a high binding affinity for bacterial genomic DNA and a strong ability to disrupt bacterial cell walls and membranes.

Anti-MRSA agent 1 is an MRSA inhibitor with an MIC value of 0.5 μg/mL and is effective in alleviating the effects of MRSA resistance.

Anti-MRSA agent is a potent antagonist of MRSA (MIC50: 0.38 μg/mL) with low hERG activity (IC50: 40 μM). anti-MRSA agent also has low toxicity to mammalian cells and little potential to acquire bacterial resistance.

Anti-MRSA agent 6 (compound 3q6) is a potent anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) agent with low cytoxicity for MCF-7, A549 cells [1].

Anti-MRSA Agent 8 (Compound 7g), a derivative of DAPG, exhibits potent antibacterial properties by interacting with bacterial cell membranes and is useful for studying methicillin-resistant Staphylococcus aureus (MRSA) [1].

Ceftobiprole (Ro 63-9141) is a broad-spectrum cephalosporin with activity against Methicillin-resistant staphylococcus aureus (MRSA; MIC90: 2 μg/mL).

Mupirocin calcium hydrate is an antibiotic produced by Pseudomonas fluorescens, showed a high level of activity against staphylococci and streptococci and against certain gram-negative bacteria

Glycosyltransferase-IN-1 is a glycosyltransferase inhibitor with bacteriostatic activity, inhibiting MSSA, MRSA, Bacillus subtilis, and Enterobacteriaceae.

Alalevonadifloxacin is a DNA gyrase and DNA topoisomerase inhibitor and a novel antibacterial compound of the quinolone class targeting MRSa. Alalevonadifloxacin is potentially useful in the treatment of bacterial Gram-positive, Gram-negative and anaerobic infections.

Robenidine hydrochloride (Robenidine Hydrochoride) is an anticoccidial agent mainly used in poultry.

Povidone iodine (Povidone-iodine) exhibits superior antibacterial properties, effectively targeting both MRSA and MSSA strains with minimum inhibitory concentrations (MICs) of 31.25 mg/L and 7.82 mg/L, respectively.

Picrasidine S shows the potent cytotoxicity against human HeLa cervical, gastric MKN-28, and mouse melanoma B-16 cancer cells, it also shows the potent antibacterial activity against two strains of pathogenic bacteria methicillin-resistant Staphylococcus

Antibacterial agent 162 trifluoromethanesulfonate (compound 7), a dual-function molecule, demonstrates potent inhibitory effects on Staphylococcus aureus, encompassing MRSA strains, and exerts antiproliferative activity against colon cancer and non-small cell lung cancer cells. This compound is applicable in both anticancer and antibacterial research [1].

Ceftaroline fosamil hydrate acetate is a powerful cephalosporin antibiotic that exhibits broad-spectrum efficacy against both Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae, and common Gram-negative bacteria. It possesses anti-infective properties suitable for studying complicated skin and skin structure infections (cSSSIs) and community-acquired bacterial pneumonia (CABP) [1] [2] [3].

Pristinamycin, synthesized by Streptomyces pristinaespiralis, is an orally administered antibiotic resembling streptogramin, comprising two distinct components: Pristinamycin I (PI) and Pristinamycin II (PII). This compound exhibits a high efficacy against various antibiotic-resistant pathogens, especially Gram-positive bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant S. aureus (VRSA), and Enterococcus faecium (VREF) [1].

Chrysomycin A is an antibiotic that can be derived from Streptomyces. Chrysomycin A, Chrysomycin A inhibits cancer cell proliferation, migration, and invasion through the Akt/GSK-3β/β-catenin signaling pathway. Exhibits antitumor antituberculosis and MRSA activity.

Viquidacin ( NXL-101) is an oral/intravenous antibiotic that targets Gram-positive bacteria such as MRSA. In 2008, Novexel announced it had discontinued the development of Viquidacin (NXL 101).

PSMα3 TFA is a peptide utilized in directing dendritic cells (DCs) towards a tolerogenic state, pivotal for DC vaccination approaches. It intrudes and recalibrates human monocyte-derived DCs, disrupting maturation triggered by TLR2 or TLR4, suppressing both pro-inflammatory and anti-inflammatory cytokine secretion, and diminishing antigen assimilation. Notably, PSMα3 TFA constitutes a significant toxin secreted by highly virulent methicillin-resistant Staphylococcus aureus (MRSA) strains [1] [2].

Antibacterial agent 163 (compound 1), a hydroxyquinoline derivative, potently inhibits methicillin-resistant Staphylococcus aureus (MRSA) [1].

Ceftaroline fosamil (TAK-599) inner salt, a cephalosporin derivative, is an N-phosphono prodrug of anti-methicillin-resistant Staphylococcus aureus (MRSA) T-91825. Ceftaroline fosamil inner salt can be used for the research of MRSA infection.

Benzyldodecyldimethylammonium chloride dihydrate can be used as an insecticide reagent. It can target drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus, multidrug-resistant Pseudomonas aeruginosa, etc., in a concentration-dependent manner.

6-Methoxydihydrosanguinarine is a natural product. 6-Methoxydihydrosanguinarine shows strong cytotoxicity against MCF-7 and SF-268 cell lines with IC50 values of 0.61 μM and 0.54 μM, respectively.It has antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentrations (MICs) ranging from1.9 to 3.9 microg/ml

TPU-0037A is an antibiotic and a congener of lydicamycin . It inhibits the growth of Gram-positive bacteria, including methicillin-resistant S. aureus (MRSA), B. subtilis, and M. luteus (MICs = 1.56-12.5 μg/ml), but not Gram-negative E. coli, P. mirabilis, P. vulgaris, or P. aeruginosa strains (MICs = >50 μg/ml).

Diallyl tetrasulfide is an organosulfur compound that has been found in A. sativum and has diverse biological activities, including antimicrobial, antioxidant, and anticancer properties.[1],[2],[3],[4] It is active against the bacteria S. aureus and methicillin-resistant S. aureus (MRSA; MICs = 0.5 and 2 mg/L, respectively), as well as the fungi C. albicans, C. krusei, C. glabrata, A. niger, A. flavus, and A. fumigatus (MICs = 0.5, 4, 2, 1, 2, and 4 mg/L, respectively).[1] It reduces cadmium-induced increases in hepatic levels of thiobarbituric acid reactive substances (TBARS) and increases cadmium-induced decreases in the hepatic activity of superoxide dismutase (SOD1), catalase, GST, and glucose-6-phosphate dehydrogenase (G6PDH) in rats when administered at a dose of 40 mg/kg.[2] Diallyl tetrasulfide is cytotoxic to MCF-7 breast cancer cells (IC50 = 92 μM) and reduces tumor growth in a BGC-823 mouse xenograft model when administered at doses of 20, 30, and 40 mg/kg for 32 days.[3],[4]

Emeguisin A is a depsidone fungal metabolite originally isolated fromE. unguis.1It is active against the bacteriaS. aureusand methicillin-resistantS. aureus(MRSA; MIC = 0.5 μg/ml for both), the fungusC. neoformans(MIC = 0.5 μg/ml), and the protozoanP. falciparum(IC50= 2.2 μM).2 1.Kawahara, N., Nozawa, K., Nakajima, S., et al.Isolation and structures of novel fungal depsidones, emeguisins A, B, and C, from Emericella unguisJ. Chem. Soc., Perkin Trans. 12611-2614(1988) 2.Klaiklay, S., Rukachaisirikul, V., Aungphao, W., et al.Depsidone and phthalide derivatives from the soil-derived fungus Aspergillus unguis PSU-RSPG199Tetrahedron Lett.57(39)4348-4351(2016)

Anacardic acid diene is a polyunsaturated form of anacardic acid that has been found in cashew nut shell liquid. It has antibacterial activity against methicillin resistant S. aureus (MRSA) and S. mutans (MICs = 12.5 and 6.25 μg/ml, respectively). Anacardic acid diene has schistosomicidal activity against adult S. mansoni worms when used at a concentration of 100 μM. It also inhibits soybean lipoxygenase-1 in a time-dependent manner.

PK150 shows oral bioavailability and antibacterial activity against several pathogenic strains at submicromolar concentrations.

Sanguisorbigenin (Tomentosolic acid) is a natural antimicrobial agent that inhibits methicillin-resistant Staphylococcus aureus (MRSA).

PSMα3 is a peptide compound that can be utilized to induce tolerance in dendritic cells (DCs) for DC vaccination strategies. It effectively penetrates and modulates human monocyte-derived DCs by modifying the maturation process induced by TLR2 or TLR4. Additionally, PSMα3 inhibits the production of both pro- and anti-inflammatory cytokines and decreases antigen uptake. Notably, PSMα3 is a significant virulence factor released by the most pathogenic strains of methicillin-resistant Staphylococcus aureus (MRSA).

(-)-Viriditoxin is a mycotoxin originally isolated from A. viridinutans that has antibacterial and antiproliferative activity. It is active against methicillin-sensitive and -resistant S. aureus (MSSA and MRSA, respectively), tetracycline-sensitive and -resistant Staphylococcus, vancomycin-sensitive and -resistant Enterococcus, and penicillin-sensitive and -resistant S. pneumoniae (MICs = 2-32 μg/ml). (-)-Viriditoxin is also active against fish pathogens, including S. iniae and S. parauberis (MICs = 0.16-0.21 μg/ml). It inhibits polymerization and the GTPase activity of E. coli FtsZ, a tubulin-like GTPase involved in bacterial cell division (IC50s = 8.2 and 7 μg/ml, respectively). (-)-Viriditoxin inhibits proliferation of human DU145, LNCaP, and PC3 prostate cancer cells (IC50s = 5.36, 0.63, and 7.6 μM, respectively) . It is also toxic to mice (LD50 = 2.8 mg/kg, i.p.).

CDFI, a lipid II flippase MurJ inhibitor, enhances the efficacy of β-lactams in combating MRSA [1] [2].

Combination of 1-acetyl-beta-carboline with ampicillin exhibits synergistic antibacterial activity against MRSA.

Juncusol shows anxiolytic and sedative activities, it shows anxiolytic activity at dosages of 10 mg/kg; it can induce caspase-3-mediated cytotoxicity in HT22 cells. Juncusol has anti-microbial activity, it shows significant activity against MRSA strains.

6-Ethoxychelerythrine (Ethoxychelerythrin) has anti-bacterial activity, it exhibited strong activity against Aspergillus fumigatus and methicillin-resistant Staphylococcus aureus (MRSA).

BIS-[6-(5,6-dihydro-chelerythrinyl)] ether shows strong activity against Aspergillus fumigatus and methicillin-resistant Staphylococcus aureus (MRSA).

CAY10742 is an orally bioavailable oxadiazole antibiotic.1It is active against the Gram-positive bacteriaS. aureus,S. epidermidis,S. haemolyticus,B. cereus,B. licheniformis,E. faecalis, andE. faecium(MICs = 1-4 μg/ml), including laboratory strains and clinical isolates with varying degrees of resistance to methicillin, vancomycin, linezolid, and other antibiotics. CAY10742 (40 mg/kg) reduces the number of bacteria in mouse neutropenic thigh models of linezolid-sensitive or -resistant methicillin-resistantS. aureus(MRSA) infection. 1.Boudreau, M.A., Ding, D., Meisel, J.E., et al.Structure-activity relationship for the oxadiazole class of antibacterialsMed. Chem. Lett.11(3)322-326(2019)

Emestrin is a mycotoxin originally isolated from E. striata that has antimicrobial, immunomodulatory, and cytotoxic activities.1,2,3,4,5 It is active against the fungi C. albicans and C. neoformans, as well as the bacteria E. coli, S. aureus, and methicillin-resistant S. aureus (MRSA; IC50s = 3.94, 0.6, 2.21, 4.55, and 2.21 μg/ml, respectively).2 Emestrin is a chemokine (C-C motif) receptor 2 (CCR2) antagonist (IC50 = 5.4 μM in a radioligand binding assay using isolated human monocytes).3 Emestrin (0.1 μg/ml) induces apoptosis in HL-60 cells.4 It induces heart, thymus, and liver tissue necrosis in mice when administered at doses ranging from 18 to 30 mg/kg.5 |1. Seya, H., Nakajima, S., Kawai, K.-i., et al. Structure and absolute configuration of emestrin, a new macrocyclic epidithiodioxopiperazine from Emericella striata. J. Chem. Soc. Chem. Commun. 10, 657-658 (1985).|2. Herath, H.M.T.B., Jacob, M., Wilson, A.D., et al. New secondary metabolites from bioactive extracts of the fungus Armillaria tabescens. Nat. Prod. Res. 27(17), 1562-1568 (2013).|3. Herath, K.B., Jayasuriya, H., Ondeyka, J.G., et al. Isolation and structures of novel fungal metabolites as chemokine receptor (CCR2) antagonists. J. Antibiot. (Tokyo) 58(11), 686-694 (2005).|4. Ueno, Y., Umemori, K., Niimi, E.-c., et al. Induction of apoptosis by T-2 toxin and other natural toxins in HL-60 human promyelotic leukemia cells. Nat. Toxins 3(3), 129-137 (1995).|5. Terao, K., Ito, E., Kawai, K.-i., et al. Experimental acute poisoning in mice induced by emestrin, a new mycotoxin isolated from Emericella species. Mycopathologia 112(2), 71-79 (1990).

Nornidulin is a depsidone originally isolated from A. nidulans that has antibacterial activity against M. tuberculosis and M. ranoe as well as antifungal activity against T. tonsurans and M. audouini. It also inhibits the growth of methicillin-resistant S. aureus (MRSA; MIC = 2 μg/ml) and has larvicidal activity toward Artemia (LC50 = 1.7 μg/ml). Nornidulin has cytotoxic activity in MOLT-3 cells (IC50 = 35.7 μM) but not HuCCA-1, HepG2, or A549 cells (IC50s = >116.4 μM).

Oritavancin is a novel semisynthetic glycopeptide antibiotics. On August 6, 2014, the FDA approved oritavancin for treatment of skin infections. Oritavancin possesses potent and rapid bactericidal activity in vitro against a broad spectrum of both resistant and susceptible Gram-positive bacteria, including Staphylococcus aureus, MRSA, enterococci, and streptococci.

Gancaonin G shows antibacterial effects on the MRSA strains with MIC values of 16 microg/ml, it also shows more moderate antibacterial activity against Streptococcus mutans.

Isolupalbigenin shows promising cytotoxic effects toward HL-60 cells (IC50 4.3 ± 0.7 to 18.0 ± 1.7 uM), it also shows in vitro inhibitory activity toward human glyoxalase I. Isolupalbigenin shows two different antibacterial activities against MRSA: direct growth inhibition and intensification of methicillin sensitivity, it could lead to the development of compounds for new approaches against MRSA infection.

IMP-1700 is an inhibitor of bacterial DNA repair.1It potentiates the activity of the quinolone antibiotic ciprofloxacin against methicillin-resistantS. aureus(MRSA) with a combination index value of 0.7. IMP-1700 inhibits the ciprofloxacin-induced bacterial SOS response, a process that repairs DNA damage, in a reporter assay in a concentration-dependent manner. It is also active againstE. coli, as well as methicillin-resistant and -sensitive S. aureus, when used alone (EC50s = 0.5, 0.21, and 3.8 μM, respectively). 1.Lim, C.S.Q., Ha, K.P., Clarke, R.S., et al.Identification of a potent small-molecule inhibitor of bacterial DNA repair that potentiates quinolone antibiotic activity in methicillin-resistant Staphylococcus aureusBioorg. Med. Chem.27(20)114962(2019)

Antibacterial agent 165 (compound 3), a hydroxyquinoline derivative, effectively inhibits methicillin-resistant Staphylococcus aureus (MRSA) [1], demonstrating its potent antibacterial properties.

Talaromycesone A is a fungal metabolite originally isolated fromTalaromyces.1It is active againstS. epidermidisand methicillin-resistantS. aureus(MRSA) bacteria (IC50s = 3.70 and 5.48 μM, respectively). Talaromycesone A inhibits acetylcholinesterase (AChE) in a cell-free assay (IC50= 7.49 μM for the human enzyme). 1.Wu, B., Ohlendorf, B., Oesker, V., et al.Acetylcholinesterase inhibitors from a marine fungus Talaromyces sp. strain LF458Mar. Biotechnol. (NY)17(1)110-119(2015)

Decatromicin B is a bacterial metabolite that has been found in Actinomadura. It is active against Gram-positive bacteria, including several strains of S. aureus (MICs = 0.39-0.78 μg/ml), two strains of methicillin-resistant S. aureus (MRSA; MICs = 0.39 and 0.78 μg/ml), as well as M. luteus, B. subtilis, and C. bovis (MICs = 0.78, 0.78, and 6.25 μg/ml, respectively).

Longistyline A (Longistylin A), a natural stilbene extracted from the leaves of Cajanus cajan, exhibits antimicrobial activity with a minimum inhibitory concentration (MIC) value of 1.56 μg/mL against MRSA and demonstrates neuroprotective effects, suggesting its potential for research in infection and neurological disorders [1] [2].

Neogambogic acid, an active ingredient in garcinia, can inhibit the growth of some solid tumors and result in an anticancer effect, it may be responsible for the inhibition of proliferation of human breast cancer cell line MCF-7 cells.

Chlorhexidine (Rotersept) is a biguanide compound used as an antiseptic agent with topical antibacterial activity. Chlorhexidine is positively charged and reacts with the negatively charged microbial cell surface, thereby destroying the integrity of the cell membrane. Subsequently, chlorhexidine penetrates into the cell and causes leakage of intracellular components leading to cell death. Since gram-positive bacteria are more negatively charged, they are more sensitive to this agent.

Chlorhexidine dihydrochloride (NSC-185) is a disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque.

Chlorhexidine digluconate is a broad-spectrum antiseptic and disinfectant with broad-spectrum antimicrobial activity, inhibits both Gram-positive and Gram-negative bacteria, induces necrosis and apoptosis, and can be used in the study of bacterial infections.

Chlorhexidine diacetate (Bactigras) is a disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque.