p-64

Risperidone (R 64 766) is a selective blocker of dopamine D2 receptors and serotonin 5-HT2 receptors that act as an atypical antipsychotic agent.

Antibacterial Agent 128, a siderophore analog-Ciprofloxacin (Ciprofloxacin) conjugate connected via a cleavable linker, demonstrates effective antibiotic properties. Specifically, it exhibits activity against P. aeruginosa and B. pseudomallei, with Minimum Inhibitory Concentration (MIC) values ranging from 0.25 to 64 μg/mL and 1 to 32 μg/mL, respectively [1].

Cys-pexiganan, a derivative of pexiganan with an added N-terminal cysteine, is an antimicrobial peptide effective against P. aeruginosa and S. aureus, with minimum inhibitory concentrations (MICs) of 64 and 16 µg/ml, respectively. Its conjugation to cellulose acetate-incorporated polyvinyl alcohol electrospun mats enhances the clotting of isolated recalcified human plasma.

LpxC-IN-5 is a potent, non-hydroxamate inhibitor of LpxC, which is an enzyme known as UDP-3-O-acyl-N-acetylglucosamine deacetylase. It exhibits an IC50 value of 20 nM. Furthermore, LpxC-IN-5 displays antibacterial activity against various strains including E. coli ATCC25922, P. aeruginosa ATCC27853, K. pneumoniae ATCC13883, and P. aeruginosa 5567. The minimum inhibitory concentration (MIC) values for these strains are 16 μg/mL, 4 μg/mL, 64 μg/mL, and 4 μg/mL, respectively.

Risperidone hydrochloride (R 64 766 hydrochloride) is a 5-HT2 receptor blocker, P-glycoprotein inhibitor, and dopamine D2 receptor antagonist, with activity on 5-HT2A (Ki: 4.8 nM) and dopamine D2 (Ki: 5.9 nM) receptors.

BING, a antimicrobial peptide discovered in Japanese medaka fish (O. laptipes), originates from vacuolar protein sorting-associated protein 13D-like (Vps13D). It exhibits efficacy against a range of Gram-negative and Gram-positive bacteria, notably including methicillin-resistant S. aureus (MRSA; MICs = 4-64 µg/ml). Furthermore, BING enhances the effectiveness of antibiotics such as ampicillin, amoxicillin, and novobiocin against P. aeruginosa, and it prevents resistance development to kanamycin and ampicillin in E. coli. Notably, its administration in vivo significantly improves survival rates in O. laptipes challenged with E. tarda.

ITH15004 is a non-nucleotide antagonist of the purinergic P2X7receptor (IC50= 9 μM in HEK293 cells expressing the human receptor).1It inhibits ATP-induced currents inX. laevisoocytes expressing the human P2X7receptor when used at a concentration of 100 μM. ITH15004 (1 μM) decreases IL-1β release from LPS-primed, ATP-stimulated isolated mouse peritoneal macrophages. It has high permeability in a parallel artificial membrane permeability assay (PAMPA). 1.Calzaferri, F., Narros-Fernández, P., de Pascual, R., et al.Synthesis and pharmacological evaluation of novel non-nucleotide purine derivatives as P2X7 antagonists for the treatment of neuroinflammationJ. Med. Chem.64(4)2272-2290(2021)

2-(1-(Thiophen-2-yl)ethylidene)hydrazinecarbothioamide is an antimicrobial agent.1It is active against the Gram-negative bacteriaE. coli,P. aeruginosa, andS. marcescens(MICs = 64, 100, and 70 μg/ml, respectively), the Gram-positive bacteriaS. aureus,M. luteus, andB. cereus(MICs = 130, 100, and 50 μg/ml, respectively), and the fungiC. albicans,G. candidum,T. rubrum,F. oxysporum,A. flavus, andS. brevicaulis(MICs = 69-120 μg/ml). 2-(1-(Thiophen-2-yl)ethylidene)hydrazinecarbothioamide is also a precursor in the synthesis of other antimicrobial agents, as well as compounds with anticancer activity.1,2 1.Youssef, M.S.K., and Abeed, A.A.O.Synthesis and antimicrobial activity of some novel 2-thienyl substituted heterocyclesHeterocycl. Commun.20(1)25-31(2014) 2.Gomha, S.M., Edrees, M.M., and Altalbawy, F.M.A.Synthesis and characterization of some new bis-pyrazolyl-thiazoles incorporating the thiophene moiety as potent anti-tumor agentsInt. J. Mol. Sci.17(9)1499(2016)

Leoidin is a depsidone originally isolated from L. gangaleoides that has antibacterial and enzyme inhibitory activities.1,2,3 It is active against the bacteria E. faecalis, H. influenzae, M. catarrhalis, S. aureus, and S. pneumoniae (MICs = 8, 32, 1, 128, and 64 μg/ml, respectively).2 Leoidin inhibits phenylalanyl-tRNA synthetase (PheRS) isolated from P. aeruginosa (IC50 = 42 μM). It also inhibits organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3 with Ki values of 0.08 and 1.84 μM, respectively, in CHO cells expressing the human transporters.3

HQNO is a natural product isolated from P. aeruginosa,and is a potent inhibitor of electron transport chain(Kd of 64 nM for complex III). It also is a potent mitochondrial NDH-2 inhibitorin many species.

Urotensin II is a peptide vasoconstrictor and agonist of the urotensin (UT) receptor (Ki= 2.06 nM for the human recombinant receptor expressed in HEK293 cells).1It stimulates intracellular calcium mobilization in HEK293 cells expressing human and rat UT (EC50s = 0.47 and 0.78 nM, respectively) but decreases intracellular calcium concentration in goby (G. mirabilis) enterocytes when used at a concentration of 500 nM.2Urotensin II (20 mU/ml) stimulates active sodium and chloride absorption across isolated goby posterior intestine in 5% seawater-adapted solution.3In vivo, urotensin II (1.5-150 nmol/kg) decreases diastolic blood pressure and increases heart rate in anesthetized rats.4It also reduces the pressor responses to sympathetic nerve stimulation, norepinephrine , and vasopressin in pithed rats when administered at a dose of 150 nmol/kg. 1.Ames, R.S., Sarau, H.M., Chambers, J.K., et al.Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14Nature401(6750)282-286(1999) 2.Loretz, C.A., and Assad, J.A.Urotensin II lowers cytoplasmic free calcium concentration in goby enterocytes: Measurements using quin2Gen. Comp. Endocrinol.64(3)355-361(1986) 3.Loretz, C.A., Freel, R.W., and Bern, H.A.Specificity of response of intestinal ion transport systems to a pair of natural peptide hormone analogs: Somatostatin and urotensin IIGen. Comp. Endocrinol.52(2)198-206(1983) 4.Gibson, A., Wallace, P., and Bern, H.A.Cardiovascular effects of urotensin II in anesthetized and pithed ratsGen. Comp. Endocrinol.64(3)435-439(1986)

Antibacterial Agent 135 (example 7) effectively inhibits various bacteria, including P. aeruginosa, A. baumannii, E. coli, and K. pneumoniae, with a minimum inhibitory concentration (MIC) greater than 64 μg/mL [1].

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].