p 25

P-gp Inhibitor 25 (compound 16c) is a P-gp inhibitor that enhances the oral absorption of paclitaxel. It is utilized in cancer research to improve treatment efficacy.

CGP 25454A is a novel and selective antagonist of the presynaptic dopamine autoreceptor (CGP 25454A).

ABP 25 is a highly potent and selective activity-based probe (ABP) for cathepsin K imaging.

3-epi-25-hydroxy Vitamin D3 is the C-3 epimer of 25-hydroxy vitamin D3. Dietary administration of 3-epi-25-hydroxy vitamin D3 (0.5 and 1 IU g) decreases levels of serum parathyroid hormone (PTH) in male, but not female, weanling rats.

Ajoene is a disulfide that has been found inA. sativumand has diverse biological activities, including antibacterial, anticancer, antiplatelet, and antioxidant properties.1,2,3,4It is active against Gram-positive (MICs = 5-160 µg/ml) and Gram-negative bacteria (MICs = 136-200 µg/ml), as well as yeasts (MICs = 10-20 µg/ml).1Ajoene is cytotoxic to mouse melanoma cells (IC50= 18 µM), as well as human colon, lung, mammary, and pancreatic cancer cells (IC50s = 7-41 µM).2It reduces tumor growth in a B16/BL6 mouse model of melanoma when administered at a dose of 25 mg/kg every other day and decreases the number of lung metastases when administered prior to tumor cell inoculation at doses ranging from 1-25 mg/kg. It inhibits ADP- or collagen-induced platelet aggregation in isolated baboon platelets when used at concentrations ranging from 75 to 150 µg/ml and in platelet-rich plasma isolated from baboons when administered at a dose of 25 mg/kg.3Ajoene (25 mg/kg) prevents thrombus formation on damaged arterial walls in heparinized pigs in anin situmodel of thrombogenesis.5It also reduces high-fat diet-induced hepatic steatosis, histopathological markers of liver damage, thiobarbituric acid reactive substances (TBARS) formation, and protein oxidation in a mouse model of non-alcoholic fatty liver disease (NAFLD).4 1.Naganawa, R., Iwata, N., Ishikawa, K., et al.Inhibition of microbial growth by ajoene, a sulfur-containing compound derived from garlicAppl. Environ. Microbiol.62(11)4238-4242(1996) 2.Taylor, P., Noriega, R., Farah, C., et al.Ajoene inhibits both primary tumor growth and metastasis of B16/BL6 melanoma cells in C57BL/6 miceCancer Lett.239(2)298-304(2006) 3.Teranishi, K., Apitz-Castro, R., Robson, S.C., et al.Inhibition of baboon platelet aggregation in vitro and in vivo by the garlic derivative, ajoeneXenotransplantation10(4)374-379(2003) 4.Han, C.Y., Ki, S.H., Kim, Y.W., et al.Ajoene, a stable garlic by-product, inhibits high fat diet-induced hepatic steatosis and oxidative injury through LKB1-dependent AMPK activationAntioxid. Redox Signal.14(2)187-202(2011) 5.Apitz-Castro, R., Badimon, J.J., and Badimon, L.A garlic derivative, ajoene, inhibits platelet deposition on severely damaged vessel wall in an in vivo porcine experimental modelThromb. Res.75(3)243-249(1994)

Beauvericin A is a cyclodepsipeptide and derivative of beauvericin originally isolated fromB. bassianathat has diverse biological activities.1,2,3It is active againstM. tuberculosis(MIC = 25 μg/ml) andP. falciparum(IC50= 12 μg/ml).2Beauvericin A is toxic to brine shrimp (LD100= 32 μg/ml).3 1.Gupta, S., Montillor, C., and Hwang, Y.-S.Isolation of Novel Beauvericin Analogues from the Fungus Beauveria bassianaJ. Nat. Prod.58(5)733-738(1995) 2.Nilanonta, C., Isaka, M., Kittakoop, P., et al.Antimycobacterial and antiplasmodial cyclodepsipeptides from the insect pathogenic fungus Paecilomyces tenuipes BCC 1614Planta Med.66(8)756-758(2000) 3.Shi, S., Li, Y., Ming, Y., et al.Biological activity and chemical composition of the endophytic fungus Fusarium sp. TP-G1 obtained from the root of Dendrobium officinale Kimura et MigoRec. Nat. Prod.12(6)549-556(2018)

Actinopyrone A is a pyrone isolated from S. pactum with diverse biological activities, showing selective and potent antimicrobial activity against H. pylori (MIC = 0.1 ng mL) and no activity against other Gram-negative bacteria including E. coli, K. pneumoniae, P. aeruginosa, and B. fragilis. It mildly inhibits the growth of Gram-positive bacteria and dermatophytes with MIC values ranging from <6.25 to 25 μg mL. Intravenous administration of actinopyrone A (30 μg kg) increases coronary blood flow in dogs by 196.2%.

Penicinoline is an alkaloid that has been found in Penicillium and has antimalarial, insecticidal, and anticancer activities.1,2 It is active against chloroquine-sensitive and -resistant strains of P. falciparum (IC50 = 25 μM for both).1 Penicinoline (1,000 ppm) is also active against the aphid A. gossypii.2 It inhibits proliferation of 95-D and HepG2 cancer cells (IC50s = 0.57 and 6.5 μg/ml, respectively) but not HeLa, KB, KBv200, or Hep-2 cells (IC50s = >100 μg/ml). |1. Naveen, B., Ommi, N.B., Mudiraj, A., et al. Total synthesis of penicinoline E, marinamide, methyl marinamide and their antimalarial activity. ChemistrySelect 2(11), 3256-3261 (2017).|2. Shao, C.-L., Wang, C.-Y., Gu, Y.-C., et al. Penicinoline, a new pyrrolyl 4-quinolinone alkaloid with an unprecedented ring system from an endophytic fungus Penicillium sp. Bioorg. Med. Chem. Lett. 20(11), 3284-3286 (2010).

Enopeptin A, originally isolated from a culture broth of Streptomyces sp. RK-1051, is a depsipeptide antibiotic containing two unusual amino acids (N-methylalanine and 4-methylproline) and features a pentaenone side chain. It is effective against Gram-positive bacteria, including methicillin-resistant S. aureus (MIC = 25 μg ml), and Gram-negative bacteria, including mutant forms of E. coli and P. aeruginosa (MICs = 200 μg ml); however, it is not inhibitory to fungi.

Givinostat (ITF-2357) is an HDAC inhibitor with IC50 values of 198 nM for HDAC1 and 157 nM for HDAC3.

AN3661, a potent antimalarial lead compound, targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue subunit 3 (PfCPSF3) and inhibits Plasmodium falciparum laboratory-adapted strains, Ugandan field isolates, and murine P. berghei and P. falciparum infections[1].

Cefazolin-13C2,15N is intended for use as an internal standard for the quantification of cefazolin by GC- or LC-MS. Cefazolin is a broad-spectrum cephalosporin antibiotic that is active in vitro against various Gram-positive and Gram-negative bacteria (MICs = 0.2-12.5 μg/ml). It also inhibits the growth of clinical isolates of S. aureus, E. coli, P. mirabilis, and K. pneumoniae (MICs = 0.1-25 μg/ml). In vivo, cefazolin protects against S. aureus, E. coli, and P. mirabilis infection in mice (ED50s = <0.09-1.78, 0.44-3.63, and 2.31-5.2 mg/animal, respectively). Formulations containing cefazolin have been used to treat a variety of bacterial infections.

Carbazomycin A is a bacterial metabolite that has been found in Streptomyces and has diverse biological activities.1,2It is active againstS. aureus,T. asteroides, andT. mentagrophytes(MIC = 12.5 μg ml for all), as well as the plant pathogenic fungusP. oryzae(MIC = 25 μg ml). Carbazomycin A is cytotoxic to MCF-7, KB, NCI H187, and Vero cells (IC50s = 26.2, 30.1, 18.4, and 32.6 μg ml, respectively).2 1.Sakano, K.-I., Ishimaru, K., and Nakamura, S.New antibiotics, carbazomycins A and B. I. Fermentation, extraction, purification and physico-chemical and biological propertiesJ Antibiot. (Tokyo)33(7)683-689(1980) 2.Intaraudom, C., Rachtawee, P., Suvannakad, R., et al.Antimalarial and antituberculosis substances from Streptomyces sp. BCC26924Tetrahedron67(39)7593-7597(2011)

Carbazomycin D is a bacterial metabolite that has been found inStreptomycesand has diverse biological activities.1,2It is active against the fungiT. asteroidesandT. mentagrophytes(MIC = 100 μg ml for both) and the bacteriumM. tuberculosis(IC50= 25 μg ml). Carbazomycin D is cytotoxic to MCF-7, KB, NCI H187, and Vero cells (IC50s = 21.3, 33.2, 12.9, and 34.3 μg ml, respectively).2 1.Naid, T., Kitahara, T., Kaneda, M., et al.Carbazomycins C, D, E and F, minor components of the carbazomycin complexJ. Antibiot. (Tokyo)40(2)157-164(1987) 2.Intaraudom, C., Rachtawee, P., Suvannakad, R., et al.Antimalarial and antituberculosis substances from Streptomyces sp. BCC26924Tetrahedron67(39)7593-7597(2011)

Hirsutide is a cyclotetrapeptide fungal metabolite produced by the entomopathogenic fungus Hirsutella. It has antibacterial activity against C. pyogenes, S. aureus, P. aeruginosa, and K. pneumonia (MICs = 25, 13, 6, and 21 μg/cm3, respectively). Hirsutide also has antifungal activity against C. albicans, M. audouinii, A. niger, and Ganoderma (MICs = 13, 6, 25, and 6 μg/cm3, respectively).

Defensin HNP-3 is a peptide secreted by human polymorphonuclear leukocytes (PMNs) that has antimicrobial properties. It induces lysis of mammalian cells when used at a concentration of 25 μg/mL. It also inhibits growth of E. faecalis (ED50 = 100 nM) and clinical isolates of P. aeruginosa (MIC90 = 4 μM). HNP-3 binds to recombinant HIV-1 envelope glycoprotein (gp120) and human CD4 (Kds = 52.8 and 34.9 nM, respectively). It also binds to recombinant, immobilized human surfactant protein D (SP-D; Kd = 55.7 nM) and inhibits focus formation in Madin-Darby canine kidney (MDCK) cells infected with influenza A virus (IAV).

Penipurdin A is an anthraquinone fungal metabolite originally isolated fromP. purpurogenumthat has antibacterial activity.1,2It is active againstM. tuberculosiswith a MIC value of 25 μg/ml.2 1.Xue, J., Fu, Y., Wu, P., et al.Two new anthraquinones from the soil fungus Penicillium purpurogenum SC0070J. Antibiot. (Tokyo)68(9)598-599(2015) 2.Daengrot, C., Rukachaisirikul, V., Tadpetch, K., et al.Penicillanthone and penicillidic acids A-C from the soil-derived fungus Penicillium aculeatum PSU-RSPG105RSC Adv.6(46)39700-39709(2016)

4-(N-Boc-amino)piperidine is an organic building block.1,2It has been used in the synthesis of aminopiperidine antiviral chemokine (C-C motif) receptor 5 (CCR5) antagonists and antibacterial agents. 1.Burrows, J.N., Cumming, J.G., Fillery, S.M., et al.Modulators of the human CCR5 receptor. Part 1: Discovery and initial SAR of 1-(3,3-diphenylpropyl)-piperidinyl amides and ureasBioorg. Med. Chem. Lett.15(1)25-28(2005) 2.Reck, F., Alm, R., Brassil, P., et al.Novel N-linked aminopiperidine inhibitors of bacterial topoisomerase type II: Broad-spectrum antibacterial agents with reduced hERG activityJ. Med. Chem.54(22)7834-7847(2011)

Agnuside (chasteberry oil) inhibits COX-2 (IC50: 0.026 mg ml) but exhibits less than 10% inhibition of COX-1 at this concentration. It also inhibits 46.3, 66.8, and 82.1% of P-glycoprotein (P-gp) ATPase activity at concentrations of 5, 25, and 100 μM, respectively.

Oxanosine is an analog of guanosine that has been found in S. capreolus and has diverse biological activities, including antibacterial, antiviral, and anticancer properties. It is active against a variety of bacteria, including S. flexneri, P. mirabilis, and E. coli (MICs = 6.25, 12.5, 25 µg ml, respectively, on peptone, but not nutrient, agar). Oxanosine inhibits replication of the HIV-1 strain IIIb in infected CEM and U937, but not H9, cells (EC50s = 7, 27, and >500 µg ml, respectively). It also inhibits the growth of HeLa human cervical cancer cells (IC50 = 32 µg ml) and reduces tumor growth in a murine L1210 lymphocytic leukemia model.

Compound 5a (Antibacterial agent 143) is an antibacterial agent exhibiting minimum inhibitory concentrations (MICs) of 25 μg mL against B. subtilis ATCC6633 and S. aureus ATCC6538, and 50 μg mL against P. aeruginosa ATCC13525 and E. coli ATCC35218, demonstrating its effectiveness in inhibiting bacterial growth [1].

Compound 9C [c[Arg-Arg-Arg-Arg-Nal-Nal-Nal]] demonstrates broad-spectrum efficacy against drug-resistant Gram-positive and Gram-negative bacteria. It exhibits minimum inhibitory concentrations (MICs) of 3.1 μg mL for MRSA (ATCC BAA-1556), 3.1 μg mL for S. aureus (ATCC 29213), 12.5 μg mL for P. aeruginosa (ATCC 27883), and 25 μg mL for E. coli (ATCC 25922) [1].

Bovine tracheal antimicrobial peptide, derived from the tracheal mucosa, exhibits antimicrobial efficacy against E. coli D31, K. pneumoniae 13883, S. aureus 25923, P. aeruginosa 27853, and C. albicans 14053, with respective minimum inhibitory concentration (MIC) values ranging from 12-25 μg ml for the first two pathogens, 25-50 μg ml for the following two, and 6-12 μg ml for the latter [1].

Azurin (50-77) is a peptide fragment derived from the copper-containing bacterial protein azurin, present in P. aeruginosa. It exhibits properties that regulate the cell cycle, inhibit cancer proliferation, and manage angiogenesis, proving its potential as an anticancer agent. Specifically, this compound acts as a VEGFR2 inhibitor with an IC20 of approximately 10.7 µM. At a concentration of 20 µM, it effectively induces cell cycle arrest at the G2 M phase in MCF-7 breast cancer cells, while a higher concentration of 50 µM significantly reduces the proliferation of both MCF-7 and ZR-75-1 breast cancer cell lines. Furthermore, Azurin (50-77) impedes VEGF-A-induced capillary tube formation with an IC50 of 12 µM, and alters the cellular and extracellular levels of critical signaling and structural proteins such as F-actin, focal adhesion kinase (FAK), paxillin, and platelet endothelial cell adhesion molecule-1 (PECAM-1) in human umbilical vein endothelial cells (HUVECs) at a concentration of 25 µM. Demonstrating its efficacy in vivo, Azurin (50-77) administered at 10 mg kg per day notably reduces tumor volume in an MCF-7 mouse xenograft model, highlighting its therapeutic potential.