mortality

Penciclovir (BRL 39123) is a Herpesvirus Nucleoside Analog DNA Polymerase Inhibitor. In HSV infected cells, penciclovir is phosphorylated by viral thymidine kinase and subsequently converted by cellular kinases into the active metabolite, penciclovir triphosphate, which competitively inhibits viral HSV polymerase by blocking deoxyguanosine triphosphate substrate binding. As a result, herpes viral DNA synthesis and replication are selectively inhibited.

Gizzerosine, a biogenic amine formed during feed processing, is a toxicant that induces mortality in livestock.

Zoliprofen is a potent and orally available non-steroidal anti-inflammatory agent with anti-inflammatory, antipyretic and analgesic activity, and inhibits carobolin, mycobacterium, and knife-ball protein A-induced rat paw oedema, as well as anti-rat serum-induced fracture or dorsal skin oedema. Zoliprofen is 20 times more effective than ibuprofen and fenoprofen against collagen- or arachidonic acid-induced platelet aggregation in rats and rabbits. Zoliprofen was 20 times more effective than ibuprofen and fenoprofen in inhibiting endotoxin-induced diarrhoea in mice and arachidonic acid-induced acute mortality in rabbits.

Benzthiazide (Lemazide) is used in the therapy of edema and hypertension. Like other thiazides, benzthiazide accelerates water loss from the body (diuretics). They inhibit Na+ Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.

Homovanillyl alcohol, a biological metabolite of Hydroxytyrosol, is a phenolic compound found in virgin olive oil (VOO) and wine. It exhibits high scavenging activities, protects red blood cells from hemolysis in a dose-dependent manner, and has a protective effect on cardiovascular disease and total mortality.

AM 281, a cannabinoid antagonist, reduces neurologic dysfunction and mortality rate after cecal ligation and puncture in rats.

Rupatadine (UR-12592, rupatadine) is a potent and orally available dual antagonist of PAF and histamine H1 receptors with Ki values of 0.55 μM and 0.1 μM, respectively, which provides relief of allergic symptoms and anti-inflammatory properties, and is used in allergic rhinitis and chronic urticaria.

(±)-Licarin A ((±)-trans-Dehydrodiisoeugenol), a dihydrobenzofuran neolignan formed via oxidative coupling of isoeugenol with horseradish peroxidase (HRP) enzyme, exhibits 100% parasite mortality at 200 μM.

Fervenulin is isolated from a nematicidal actinomycete Streptomyces sp. CMU-MH021 with nematicidal activity. It also inhibits egg hatch and J2 mortality of M. incognita (MICs: 30 μg mL and 120 μg mL, respectively).

UMB24 is an effective antagonist of the σ2 receptor, exhibiting dissociation constants (Ki values) of 170 nM for the σ2 receptor and 322 nM for the σ1 receptor. This compound mitigates cocaine-induced convulsions and hyperactivity without causing mortality.

APOL1-IN-2 (Compound 467) acts as an inhibitor of apolipoprotein L1 (APOL1). It effectively reduces HEK293 cell death induced by APOL1 G2 G1, with EC50 values of 4.74 nM and 14.3 nM, respectively. Additionally, APOL1-IN-2 decreases the mortality of trypanosomes triggered by APOL1 G2 G1 G0, with EC50 values of 2.24, 6.03, and 3.72 nM, respectively.

3'-Ethoxy-5,6-dihydrospinosyn J 17-pseudoaglycone is a potent insecticidal derivative of spinosyn. At a concentration of 500 mg L, it achieves a 100% mortality rate against armyworms, aphids, and red spider mites.

QKY-613 is a prodrug designed to enhance immune surveillance by targeting nucleic acid modification pathways. It selectively facilitates the incorporation of 6mdA (N6-methyl-deoxyadenosine) into viral DNA, boosting the DNA's phase separation potential and subsequently increasing cGAS activation levels to strengthen host immune surveillance. In mouse models of viral infection, QKY-613 significantly reduced mortality in aged mice. This compound holds promise for studying immune surveillance mechanisms based on nucleic acid modifications.

1,2,3,4,7,8-Hexachlorodibenzo-p-dioxin is a polychlorinated dibenzodioxin (PCDD) congener. At the highest dose (10,000 μg kg), it can cause hepatic pallor (fatty liver), gastrointestinal bleeding, and early mortality in H W and A strain rats. Additionally, 1,2,3,4,7,8-Hexachlorodibenzo-p-dioxin induces liver sinusoidal dilatation and can lead to severe purpura in B strain rats.

SRSF1-IN-1 (STP2) is an inhibitor of SRSF1 that modulates the splicing of Bcl-x precursor mRNA by downregulating SRSF1 expression. It exhibits antitumor activity in vitro and in vivo, with IC50 values ranging from 0.33 to 6.93 μM against cancer cells such as HepG2 and MCF7. In mice, SRSF1-IN-1 demonstrates a high safety profile, as intraperitoneal administration of 1 g kg does not lead to mortality or pathological damage. SRSF1-IN-1 holds potential for research in the field of antitumor therapy [1].

GSK J5 is an inhibitor of schistosomes and helminths and is often used as a trematode insecticide.GSK J5 promotes schistosome mortality in a dose- and time-dependent manner.GSK J5 increases the mortality rate of schistosomes and decreases the viability of adult worms.GSK J5 is an inhibitor of schistosomes and helminths and is often used as a trematode insecticide.

SUN-C5174 is a sleective 5-HT2 antagonist (pA2=8.98+/-0.06). SUN C5174 showed a marked inhibitory effect on the platelet aggregation induced by serotonin in combination with collagen and adenosine diphosphate (ADP) in canine or human platelet-rich plasma

Neospiramycin I is a macrolide antibiotic and derivative of spiramycin I.1It is active against the macrolide-sensitive KB210, but not the macrolide-resistant KB224, strain ofS. aureus(MICs = 3.12 and >100 μg/ml, respectively), as well asB. cereus,B. subtilis,M. luteus,E. coli, andK. pneumoniae(MICs = 1.56, 3.12, 3.12, 0.2, 50, and 12.5 μg/ml, respectively). Neospiramycin I binds toE. coliribosomes with an IC50value of 1.2 μM. It protects against mortality in a mouse model ofS. pneumoniaetype III infection (ED50= 399.8 mg/kg).2

Monocerin is a fungal metabolite that has been found inF. larvarumand has diverse biological activities.1,2,3It is active against the bacteriaE. coliandB. megaterium, the phytopathogenic fungusM. violaceum, and the algaC. fuscain an agar diffusion assay when used at a concentration of 50 μg/disc.1Monocerin (17.5 μg/ml) induces mortality in adultC. erythrocephala.2It reduces root elongation in pre-germinatedS. halepenseseeds when used at a concentration of 33 ppm.3 1.Zhang, W., Krohn, K., Draeger, S., et al.Bioactive isocoumarins isolated from the endophytic fungus Microdochium bolleyiJ. Nat. Prod.71(6)1078-1081(2008) 2.Claydon, N., Grove, J.F., and Pople, M.Insecticidal secondary metabolic products from the entomogenous fungus Fusarium larvarumJ. Invertebr. Pathol.33(3)364-367(1979) 3.Robeson, D.J., and Strobel, G.A.Monocerin, a phytotoxin from Exserohilum turcicum (Drechslera turcica)Agr. BioI. Chem.46(11)2681-2683(1982)

Tetranactin is a macrotetrolide and a monovalent cation ionophore that has been found in S. aureus and has antibacterial, insecticidal, and mitogenic activities. It exhibits an equilibrium permeability ratio 1,000-fold greater for lithium than sodium or cesium ions accross bilayer membranes at low voltages. Tetranactin inhibits the growth of Gram-positive bacteria and C. miyabeanus and R. solani fungi when used at concentrations less than 0.9 μg/ml. Tetranactin (0.5-1.5 μg per insect) dose-dependently increases the mortality of adult C. chinensis weevils up to 100% and has mitogenic activity against T. telarius when sprayed onto plants with an LC50 value of 9.2 μg/ml. It reduces IL-1β- and cAMP-induced secretion of phospholipase A2 (PLA2) from rat mesangial cells (IC50s = 43 and 33 nM, respectively). Tetranactin (50 ng/ml) suppresses the proliferation of human T lymphocytes induced by allogeneic cells and IL-2 and supresses the generation of cytotoxic T lymphocytes in mixed lymphocyte cultures. In vivo, tetranactin (10 mg/animal per day) completely inhibits the formation of experimental autoimmune uveoretinitis (EAU) in rats.

Phenylpyropene A is a fungal metabolite originally isolated from P. griseofulvum that has enzyme inhibitory and insecticidal activities.1,2,3 It inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT; IC50 = 0.8 μM).1 Phenylpyropene A inhibits diacylglycerol acyltransferase (DGAT) in rat liver microsomes (IC50 = 78.7 μM). It induces mortality in 100% of M. persicae when used at a concentration of 5 ppm.3 |1. Kwon, O.E., Rho, M.C., Song, H.Y., et al. Phenylpyropene A and B, new inhibitors of acyl-CoA: Cholesterol acyltransferase produced by Penicillium griseofulvum F1959. J. Antibiot. (Tokyo) 55(11), 1004-1008 (2002).|2. Lee, S.W., Rho, M.C., Choi, J.H., et al. Inhibition of diacylglycerol acyltransferase by phenylpyropenes produced by Penicillium griseofulvum F1959. J. Microbiol. Biotechnol. 18(11), 1785-1788 (2008).|3. Horikoshi, R., Goto, K., Mitomi, M., et al. Identification of pyripyropene A as a promising insecticidal compound in a microbial metabolite screening. J. Antibiot. (Tokyo) 70(3), 272-276 (2017).

Piericidin B is a bacterial metabolite that has been found inS. mobaraensisand has insecticidal and antimicrobial activities.1,2,3It inhibits NADH oxidase activity in isolated bovine heart mitochondria and inhibits respiration in isolated rat liver mitochondria and isolated cockroach (P. americana) muscle mitochondria.2,3Topical application of piericidin B (4 μg/insect) induces mortality in 87.5% of houseflies (M. domestica).1It induces 93.3, 100, and 100% mortality in rice stem borer (C. simples), silkworm (B. mori), and green caterpillar (P. rapae) larvae, respectively, when applied at respective concentrations of 60, 4.8, and 96 μg/larva. Piericidin B is active against the fungiT. asteroides,T. rubrum,M. gypseum, andC. neoforms(MICs = 20, 10, 20, and 2 μg/ml, respectively), as well as the bacteriaM. luteusandP. vulgaris(MICs = 50 and 100 μg/ml, respectively). 1.Takahashi, N., Suzuki, A., Kimura, Y., et al.Isolation, structure and physiological activities of piericidin B, natural Insecticide produced by a StreptomycesAgr. Biol. Chem.32(9)1115-1122(1968) 2.Jeng, M., Hall, C., Crane, F.L., et al.Inhibition of mitochondrial electron transport by piericidin A and related compoundsBiochemistry7(4)1311-1322(1968) 3.Mitsui, T., Fukami, J.-I., Fukunaga, K., et al.Studies on piericidin. I. : Effects of piericidin A and B on mitochondrial electron transport in insect muscle comparing with rotenoneSci. Insect Control34(3)126-134(1969)

Avilamycin A is an antibiotic.1 It is active against veterinary isolates of C. perfringens (MICs = ≤0.06-0.5 mg/L) and B. hyodysenteriae (MICs = 12.5-100 μg/ml).1,2 Dietary administration of avilamycin A (15 and 30 ppm) reduces mortality in a broiler cockerel model of C. perfringens infection.3 Formulations containing avilamycin A have been used in the prevention of necrotic enteritis in livestock. |1. Watkins, K.L., Shryock, T.R., Dearth, R.N., et al. In-vitro antimicrobial susceptibility of Clostridium perfringens from commercial turkey and broiler chicken origin. Vet. Microbiol. 54(2), 195-200 (1997).|2. Uezato, K., Kinjo, E., and Adachi, Y. In vitro susceptibility of 21 antimicrobial agents to 37 isolates of Brachyspira hyodysenteriae isolated from pigs in Okinawa Prefecture. J. Vet. Med. Sci. 66(3), 307-309 (2004).|3. Paradis, M.A., McMillan, E., Bagg, R., et al. Efficacy of avilamycin for the prevention of necrotic enteritis caused by a pathogenic strain of Clostridium perfringens in broiler chickens. Avian Pathol. 45(3), 365-369 (2016).

6'7'-Epoxybergamottin is a furanocoumarin found in grapefruit. It is a potent inhibitor of the cytochrome P450 (CYP) isoform CYP3A4 with an IC50 value of 0.30 ppm in a cell-free assay, 0.33 μM in HL7 human liver cells, and 0.22 μM in S9 human intestine cells. It has been studied in the context of drug interactions with grapefruit constituents. It is found in grapefruit juice at concentrations of 0.1-7.4 μM and inhibits the transport of talinolol , a permeability glycoprotein (P-gp/ABCB1) transporter substrate, across Caco-2 cell monolayers (IC50 = 0.7 μM). 6'7'-Epoxybergamottin also has insecticidal properties with a concentration of 5 μg/cm2 leading to 100% mortality of adult olive fruit flies.