mic-10

Mahanimbine 存在于Murraya koenigii 的根、叶和茎中，是从Murraya koenigii 中的提取的一种具有口服活性的生物碱。Mahanimbine 具有乙酰胆碱酯酶抑制活性，可抑制了高脂肪饮食（HFD）引起的小鼠代谢并发症的发展，对科尼氏分枝杆菌叶对链脲佐菌素诱导的糖尿病大鼠胰腺β细胞组织病理学变化有作用。

Chlamydia pneumoniae-IN-1 是一种对衣原体有抑制作用的苯并咪唑类化合物，在低浓度下即可对肺炎衣原体产生抑制作用。Chlamydia pneumoniae-IN-1 具有抗菌活性，对CV-6菌株的 MIC 为12.6 μM，可用于研究肺部感染。

2,6-Dichlorodiphenylamine 是双氯芬酸钠的一种结构类似物，显示出抗白色念珠菌活性。2,6-Dichlorodiphenylamine 是非选择性抗炎剂，为COX 的抑制剂，在 CHO 细胞中，对人 COX-1 和 COX-2 的IC50分别为 4 和 1.3 nM。

Quinine sulfate dihydrate 在钾通道阻滞剂中起主要作用。它也被用作抗疟疾、抗胆碱能、抗高血压和降糖药。它抑制线粒体atp 调节的钾通道。它也被用来研究生物结晶血红素，血红素，在疟疾寄生虫的代谢和研究血红素(FP)复合物的毒性。

Antifungal agent 114 (Compound 19g) 作为一种强效的细胞色素 P450 (Cytochrome P450) 抑制剂，在10 μM 浓度下能够有效抑制 CYP2C9、CYP2C19、CYP2D6 和 CYP3A4。此外，该化合物对 Cryptococcus neoformans、Candida 和 Aspergillus 显示出显著的抗真菌活性，其最小抑菌浓度（MIC）低于0.0625 μg mL。在人类肝微粒体中，Antifungal agent 114 展现出优良的代谢稳定性，其半衰期达到107分钟。

GuaB-IN-1 (Compound 15) 对 M.tb 表现出有效性，MIC 为 0.25 μM。在 10 μM 浓度下，GuaB-IN-1 对 hERG 的抑制率为 28%。GuaB-IN-1 适用于结核病的研究。

抗菌剂-38 (compound 10) 是对甲氧西林耐药金黄色葡萄球菌 (S. aureus) ATCC 700699 和非耐药菌株 ATCC 29213 的有效抑制剂，最低抑菌浓度 (MIC) 分别为 32 mg L 和 64 mg L。

Dactylfungins A is a novel antifungal antibiotic produced by Dactylaria Parvispora. The antibiotics were active against Candida pseudotropicalis and other fungi, with a MIC value of fewer than 10 micrograms ml.

Dactylfungins B is a novel antifungal antibiotic produced by Dactylaria Parvispora. The antibiotics were active against Candida pseudotropicalis and other fungi, with a MIC value of fewer than 10 micrograms ml.

Leucomycin a5 is a metabolite from the leucomycin complex, which was originally isolated from S. kitasatoensis. It is active against a variety of Gram-positive and Gram-negative bacteria (MICs = 0.04-0.8 µg ml) but not against K. pneumoniae, S. typhimuriu

(+)-δ-Cadinene 是一种从G. hirsutum 中发现的倍半萜，具有抗菌、杀虫、抗癌和抗增殖活性。 它对肺炎双球菌的MIC 值为31.25 μg ml，对 A. stephensi、A. aegypti 和 C. quinquefasciatust 三龄幼虫的LC50s 值分别8.23、9. 2和3。(+)-δ-Cadinene（10、50 和 100 μM）可诱导 OVCAR-3 人类卵巢癌细胞凋亡并抑制其增殖。

β-Defensin-4 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts. It induces migration of monocytes in vitro when used at a concentration of 10 nM but does not affect migration of neutrophils and eosinophils. β-Defensin-4 (30 μg/ml) stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes. It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 10, and 40 μg/ml, respectively. β-Defensin-4 induces IL-31 production by human peripheral blood-derived mast cells in vitro when used at a concentration of 10 μg/ml and by rat mast cells in vivo following a 500 ng intradermal dose. It also inhibits growth of E. coli, P. aeruginosa, and S. aureus with lethal concentration (LC) values of 5, 12, and 15 μM, respectively, of S. carnosus (MIC = 4.5 μg/ml), and of C. albicans with a minimum fungicidal concentration (MFC) value of 7.5 μM.

19,20-Epoxycytochalasin D is a fungal metabolite that has been found in the endophytic fungus Nemania sp. UM10M. It is active against the chloroquine-sensitive and -resistant strains of P. falciparum (MIC = 0.4 ng ml for both) without inducing cytotoxicity in Vero cells. It is cytotoxic to BT-549, LLC-PK11, and P388 cells (IC50s = 7.84, 8.4, and 0.16 µM, respectively) but not SK-MEL, KB, or SKOV3 cells up to a concentration of 10 µM.

Gliovirin is a fungal metabolite that has been found inT. harzianumand has fungicidal, antimicrobial and anti-inflammatory activities.1It is active against the plant pathogenic fungusP. ultimum(MIC = 60 ng/ml) and the parasiteT. brucei brucei(IC50= 90 ng/ml), but has no effect on the plant pathogenic fungiR. solani,P. omnivorum,T. basicola,R. arrhizus, andV. dahliaeor the bacteriaB. thuringiensis,P. fluorescens, andX. malvacearumwhen used at concentrations up to 1,000 ng/ml.2,3Gliovirin decreases phorbol 12-myristate 13-acetate (TPA)- and ionomycin-induced increased expression of COX-2 (IC50= 1 μM) and protein levels of IL-2 in Jurkat cells (IC50= 5.2 μM).1 1.Rether, J., Serwe, A., Anke, T., et al.Inhibition of inducible tumor necrosis factor-α expression by the fungal epipolythiodiketopiperazine gliovirinBiol. Chem.388(6)627-637(2007) 2.Howell, C.R., and Stipanovic, R.D.Gliovirin, a new antibiotic from Gliocladium virens, and its role in the biological control of Pythium ultimumCan. J. Microbiol.29(3)321-324(1983) 3.Iwatsuki, M., Otoguro, K., Ishiyama, A., et al.In vitro antitrypanosomal activity of 12 low-molecular-weight antibiotics and observations of structure/activity relationshipsJ. Antibiot. (Tokyo)63(10)619-622(2010)

Roccellic acid is a lichen secondary metabolite that has been found in R. montagnei and has antibacterial and anticancer activities.1,2 It is active against the bacteria S. gordonii and P. gingivalis (MIC = 46.9 μg/ml for both).1 Roccellic acid (100 μg/ml) inhibits proliferation of MDA-MB-231, MCF-7, and DLD-1 cancer cells by 65.3, 75.8, and 87.9%, respectively.2 |1. Sweidan, A., Chollet-Krugler, M., Sauvager, A., et al. Antibacterial activities of natural lichen compounds against Streptococcus gordonii and Porphyromonas gingivalis. Fitoterapia 121, 164-169 (2017).|2. Mishra, T., Shukla, S., Meena, S., et al. Isolation and identification of cytotoxic compounds from a fruticose lichen Roccella montagnei, and it's in silico docking study against CDK-10. Rev. Bras. Farmacogn. 27(6), 724-728 (2017).

TunR2 is an antibiotic and derivative of tunicamycin .1It is active againstB. subtilis(MIC = 0.3 μg ml) and increases the efficacy of the β-lactam antibiotics oxacillin , methicillin , and penicillin G againstB. subtiliswhen used at a concentration of 0.4 μg ml. Unlike tunicamycin, TunR2 is non-toxic toS. cerevisiae(MIC = >10 μg ml) and does not inhibit glycosylation in a protein N-glycosylation assay. TunR2 also has reduced antiproliferative activity against MDA-MB-231 and CHO cells compared with tunicamycin. 1.Price, N.P., Hartman, T.M., Li, J., et al.Modified tunicamycins with reduced eukaryotic toxicity that enhance the antibacterial activity of β-lactamsJ. Antibiot. (Tokyo)70(11)1070-1077(2017)

Nocardamine is a ferrioxamine siderophore that has been found inStreptomycesand has diverse biological activities.1,2,3,4It chelates iron in a chrome azurol S assay (IC50= 9.9 μM).1Nocardamine inhibitsM. smegmatisandM. bovisbiofilm formation (MIC = 10 μM for both), an effect that can be reversed by iron.2It is cytotoxic to T47D, SK-MEL-5, SK-MEL-28, and RPMI-7951 cancer cells (IC50s = 6, 18, 12, and 14 μM, respectively).3Nocardamine also induces morphological changes in BM-N4 insect cells.4 1.Lopez, J.A.V., Nogawa, T., Futamura, Y., et al.Nocardamin glucuronide, a new member of the ferrioxamine siderophores isolated from the ascamycin-producing strain Streptomyces sp. 80H647J. Antibiot. (Tokyo)72(12)991-995(2019) 2.Ishida, S., Arai, M., Niikawa, H., et al.Inhibitory effect of cyclic trihydroxamate siderophore, desferrioxamine E, on the biofilm formation of Mycobacterium speciesBiol. Pharm. Bull.34(6)917-920(2011) 3.Kalinovskaya, N.I., Romaneko, L.A., Irisawa, T., et al.Marine isolate Citricoccus sp. KMM 3890 as a source of a cyclic siderophore nocardamine with antitumor activityMicrobiol. Res.166(8)654-661(2011) 4.Matsubara, K., Sakuda, S., Tanaka, M., et al.Morphological changes in insect BM-N4 cells induced by nocardamineBiosci. Biotechnol. Biochem.62(10)2049-2051(1998)

Boromycin is a boron-containing macrolide antibiotic that has been found in Streptomyces. Boromycin inhibits growth of B. subtilis (MIC = 0.05 μg ml) and induces efflux of potassium ions from B. subtilis without affecting Na+ K+-ATPase activity. It decreases the synthesis of protein, RNA, and DNA in B. subtilis when used at a concentration of 0.05 μg ml. It inhibits the growth of B. halodurans (MIC = 10 ng ml) and inhibits the futalosine pathway of menaquinone synthesis in B. halodurans. Boromycin (3.4 nM) reverses bleomycin-induced cell cycle arrest at the G2 phase in Jurkat cells. It inhibits replication of the HIV-1 strains LAV-1 and RF and the HIV-2 strain LAV-2 in MT-4 cells (IC50s = 0.008, 0.11, and 0.007 μM, respectively). It also inhibits replication of a clinical isolate of HIV-1, strain KK-1, in MT-4 cells and peripheral blood mononuclear cells (PBMCs; IC50s = 0.14 and <0.1 μM, respectively).

Funalenone is a phenalenone originally isolated from A. niger. It inhibits HIV-1 integrase (IC50 = 10 μM) and HIV-1 replication in human peripheral blood cells transformed by murine leukemia virus (HPB-M(a); IC50 = 1.7 μM) but is less cytotoxic to mammalian HPB-M(a) cells (IC50 = 87 μM). Funalenone selectively inhibits matrix metalloproteinase-1 (MMP-1; IC50 = 170 μM) over MMP-2 and MMP-9, which it inhibits by 18.3 and 38.2%, respectively, when used at a concentration of 400 μM. It also inhibits the bacterial cell wall synthesis enzymes MraY and MurG (IC50s = 25.5 μM in a membrane plate assay) and inhibits growth of S. aureus with a MIC value of 64 μg mL.

IT-143A is a bacterial metabolite originally isolated fromStreptomycessp. IT-143.1It is active against the bacteriumM. luteus(MIC = 6.25 μg/ml) and the fungiA. fumigatusandT. rubrumin vitro(MICs = 12.5-25 μg/ml). 1.Urakawa, A., Sasaki, T., Yoshida, K., et al.IT-143-A and B, novel piericidin-group antibiotics produced by Streptomyces SpJ. Antibiot. (Tokyo)49(10)1052-1055(1996)

OPC-167832 is a potent and orally active dprE1 Inhibitor with an IC50 of 0.258 μM. OPC-167832 has antituberculosis activity and can be used for the research of tuberculosis caused by Mycobacterium tuberculosis[1]. OPC-167832 exhibits very low MICs against laboratory strains of M. tuberculosis H37Rv (MIC: 0.0005 μg ml) and Kurono (MIC: 0.0005 μg ml) and strains with monoresistance to rifampin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and pyrazinamide (PZA) (MIC: 0.00024-0.001 μg ml). However, OPC-167832 has minimal or no activity against standard strains of nonmycobacterial aerobic and anaerobic bacteria[1].The IC90 values of OPC-167832 against intracellular M. tuberculosis strains H37Rv and Kurono are 0.0048 and 0.0027 μg ml, respectively. OPC-167832 shows bactericidal activity against intracellular M. tuberculosis at a low concentration, and the bactericidal activity is saturated at concentrations of 0.004 μg ml or higher[1]. OPC-167832 (oral administration; 0.625-10 mg kg) exhibits a good pharmacokinetic characteristic. The plasma reaches peak at 0.5 h to 1.0 h (tmax) and is eliminated with a half-life (t1 2) of 1.3 h to 2.1 h OPC-167832 distribution in the lungs is approximately 2 times higher than that in plasma, and the Cmax and AUCt of OPC-167832 in plasma and the lungs shows dose dependency[1].OPC-167832 (oral administration; 0.625-10 mg kg; 4 weeks) significantly reduces lung CFU compared to the vehicle group. The dose-dependent decrease of lung CFU is observed from 0.625 mg kg to 2.5 mg kg. In a M. tuberculosis Kurono-infected ICR female mice model. OPC-167832 combines with DMD, BDQ, or LVX via oral gavage exhibits significantly higher efficacies than each single agent alone[1].[1].OPC-167832 (oral gavage; 2.5 mg kg; combination with DCMB; 12 weeks) demonstrates the most potent efficacy when compares with DC, DCB. The lung CFU count after 6 weeks of treatment is below the detection limit, and at the end of just 8 weeks of treatment, the bacteria in the lungs of all the evaluated mice had already been eradicate[1]. [1]. Norimitsu Hariguchi, et al. OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor.Antimicrob Agents Chemother. 2020 May 21;64(6):e02020-19.

Kocurin is a thiazolyl peptide originally isolated fromK. palustrisand has antibiotic activity.1It is active against methicillin-resistantS. aureus(MRSA; MIC = 0.25 μg ml), as well asB. subtilisandE. faeciumin a solid agar test when used at a concentration of 8 μg ml. Kocurin is also active againstE. faecium,E. faecalis,S. epidermidis, and clinical isolates of vancomycin-resistant enterococci (MICs = 0.004-1.025 μg ml).2In vivo, kocurin (2.5, 5, and 10 mg ml) increases survival in a mouse model ofE. faecium-induced septicemia. It decreases the number of colony forming units (CFUs) in a mouse model of MRSA lung infection. 1.Martin, J., da S. Sousa, T., Crespo, G., et al.Kocurin, the true structure of PM181104, an anti-methicillin-resistant Staphylococcus aureus (MRSA) thiazolyl peptide from the marine-derived bacterium Kocuria palustrisMar. Drugs11(2)387-398(2013) 2.Mahajan, G., Thomas, B., Parab, R., et al.In vitro and in vivo activities of antibiotic PM181104Antimicrob. Agents Chemother.57(11)5315-5319(2013)

Leucomycin A13 is a macrolide antibiotic and a component of the leucomycin complex originally isolated from S. kitasatoensis. It is active against B. subtilis, S. aureus, M. luteus, and E. coli with MIC values of 0.16, 0.16, 0.08 and >10 μg ml, respectively. It binds to ribosomes with an IC50 value of 1.2 μM in a radioligand binding assay.

Antitubercular agent-10 shows potent antitubercular activity with a MIC value of 30 nM.