Argatroban is a direct, selective thrombin inhibitor.Target: ThrombinArgatroban may have a complementary effect for preventing thrombus formation without aggravating bleeding tendency because of its monotarget specificity to thrombin. Administration (0.5 to 2 micrograms/kg/min) of argatroban is a safe anticoagulant for left heart bypass in repairs of traumatic aortic rupture associated with multiple organ injuries [1]. Argatroban, as compared with heparin, appears to enhance reperfusion with TPA in patients with AMI, particularly in those patients with delayed presentation. The incidences of major bleeding and adverse clinical outcome were lower in the patients receiving argatroban [2].
Cytidine is a nucleoside molecule that is formed when cytosine is attached to a ribose ring, cytidine is a component of RNA.Target: Nucleoside antimetabolite/analogCytidine is a nucleoside molecule that is formed when cytosine is attached to a ribose ring (also known as a ribofuranose) via a β-N1-glycosidic bond. Cytidine is a component of RNA. If cytosine is attached to a deoxyribose ring, it is known as a deoxycytidine. Dietary sources of cytidine include foods with high RNA (ribonucleic acid) content, such as organ meats, Brewer's yeast, as well as pyrimidine-rich foods such as beer. During digestion, RNA-rich foods are broken-down into ribosyl pyrimidines (cytidine and uridine), which are absorbed intact. In humans, dietary cytidine is converted into uridine, which is probably the compound behind cytidine's metabolic effects.There are a variety of cytidine analogs with potentially useful pharmacology. For example, KP-1461 is an anti-HIV agent that works as a viral mutagen, and zebularine exists in E. coli and is being examined for chemotherapy. Low doses of azacitidine and its analog decitabine have shown results against cancer through epigenetic demethylation.
Dihydrochelerythrine is a natural compound isolated from the leaves of Macleaya microcarpa; has antifungal activity.IC50 value:Target: in vitro: Dihydrochelerythrine showed the highest antifungal activity against B. cinerea Pers, with 98.32% mycelial growth inhibition at 50 μg/mL. Dihydrochelerythrine inhibited spore germination in vitro in a concentration-dependent manner [1]. Dihydrochelerythrine appeared to be less cytotoxic since the viability of cells exposed to 20 microM dihydrochelerythrine for 24h was reduced only to 53%. A dose-dependent induction of apoptosis and necrosis by chelerythrine and dihydrochelerythrine was confirmed by annexin V/propidium iodide dual staining flow cytometry [2]. Dihydrochelerythrine (4) exhibited strong activity against methicillin-resistant Staphylococcus aureus SK1 and moderate activity against Escherichia coli TISTR 780 with MIC values of 8 and 16 μg/mL, respectively [3].
Setiptiline is a serotonin receptor antagonist.IC50 value:Target: 5-HT receptorSetiptiline is a tetracyclic antidepressant (TeCA) which acts as a noradrenergic and specific serotonergic antidepressant (NaSSA). Setiptiline acts as a norepinephrine reuptake inhibitor, α2-adrenergic receptor antagonist, and serotonin receptor antagonist, likely at the 5-HT2A, 5-HT2C, and/or 5-HT3 subtypes, as well as an H1 receptor inverse agonist/antihistamine. From Wikipedia.
Theobromine is a methylxanthine found in cacao beans which can inhibit adenosine receptor A1 (AR1) signaling.
2-Benzoxazolinone is an anti-leishmanial agent with an LC50 of 40 μg/mL against L. donovani[1]. A building block in chemical synthesis. 1,3-Benzoxazol-2(3H)-one derivatives have antimicrobial activity against a selection of Gram-positive, Gram-negative bacteria and yeasts[3]. Derivatives as anti-quorum sensing agent[4].
Hydrastine is a natural alkaloid which is present in Hydrastis canadensis and other plants of the ranunculaceae family.
Ellipticine hydrochloride is a potent antineoplastic agent; inhibits DNA topoisomerase II activities.
Atropine sulfate monohydrate is a competitive muscarinic acetylcholine receptor antagonist.Target: mAChRAtropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna), Jimson weed (Datura stramonium), mandrake (Mandragora officinarum) and other plants of the family Solanaceae. Atropine is a competitive antagonist of the muscarinic acetylcholine receptors (acetylcholine being the main neurotransmitter used by the parasympathetic nervous system). Atropine dilates the pupils, increases heart rate, and reduces salivation and other secretions [1].
(+)-Bicuculline is a light-sensitive competitive antagonist of GABA-A receptor.
Nifuratel(NF 113, SAP 113) is a broad antibacterial spectrum agent, which is used as an antibacterial, antifungal, and antiprotozoal (Trichomonas).IC50 Value: 0.125-1 μg/mL(MIC, A. vaginae) [1]Target: Antibacterial; Antiprotozoal in vitro: In vitro, nifuratel is able to inhibit the growth of A. vaginae, with a MIC range of 0.125-1 μg/mL; it is active against G. vaginalis and does not affect lactobacilli [1].in vivo: Patients were randomized to receive a 2-week course of bismuth subcitrate (8 mg/kg/day, q.d.s.), amoxicillin (50 mg/kg/day, q.d.s.), with either nifuratel (15 mg/kg/day, q.d.s.) or furazolidone (10 mg/kg/day, q.d.s.), plus omeprazole (0.5 mg/kg, once daily) [2].Toxicity: There were no serious adverse reactions and were no withdrawals due to any side-effects. All of side-effects were self-limiting (dark stools, urine discoloration, blackening of the tongue, and others) [3].Clinical trial: N/A
Brofaromine is a monoamine oxidase (MAO) inhibitor with IC50 of 0.2 μM for MAO-A.
Lappaconitine, isolated from Aconitum sinomontanum Nakai, was characterized as analgesic principle.IC50 value:Target:In vitro: In vivo: Lappaconitine was characterized as analgesic principle by our laboratory. The results suggest that lappaconitine can produce analgesia, possibly through a decrease in cellular calcium availability and PAG may be involved in the Ca2+ antagonistic effect on lappaconitine analgesia [1]. Changes in lappaconitine levels in blood, brain and spinal cord following subcutaneous (s.c.) injection were correlated with the analgesic activity at intervals up to 90 minutes after injection. The equianalgesic doses of lappaconitine (ED50 by the s.c. route and additive ED50 by the i.c.v. plus i.t. route) gave closely similar concentrations of the drug in brain and spinal cord. These results indicate that a simultaneous action of lappaconitine on supraspinal and spinal sites is likely to be important for the analgesia produced by systemically administered lappaconitine [2].
Oxymatrine, an alkaloid from the roots of Sophora species, with anti-inflammatory, antifibrosis, and antitumor effects, inhibits the iNOS expression and TGF-β/Smad pathway.
Scopolamine is a high affinity (nM) muscarinic antagonist. 5-HT3 receptor-responses are reversibly inhibited by Scopolamine with an IC50 of 2.09 μM.
Tetrahydropalmatine, an active component isolated from corydalis, acts through inhibition of amygdaloid release of dopamine to inhibit an epileptic attack in rats.
N-Benzylpalmitamide is a macamide isolated from Lepidium meyenii, acts as an inhibitor of fatty acid amide hydrolase (FAAH).
Celgosivir (MBI 3253; MDL 28574; MX3253) is a novel α-glucosidase I inhibitor, an enzyme that plays a critical role in viral maturation by initiating the processing of the N-linked oligosaccharides of viral envelope glycoproteins.[1]
Cefsulodin sodium salt hydrate is a third generation β lactam antibiotic and member of the cephems subgroub of antibiotics. Target: AntibacterialThe compound displays a mechanism of action like many β lactam antibiotics through inhibition of cell wall synthesis by competitively inhibiting penicillin binding protein (PBP) crosslinking of peptidoglycan resulting in inhibition of the final transpeptidation step. Through the inability for Cefsulodin sodium salt hydrate to inhibit cefsulodin-resistant mutants of Pseudomonas aeruginosa PAO4089 growth displayed that Cefsulodin sodium salt hydrate may compete with PBP3 in addtion to PBP1A and PBP1B.
L-(+)-Abrine, a lethal albumin found in Abrus precatorius seeds, is an acute toxic alkaloid and chemical marker for abrin.
Norfloxacin hydrochloride is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria, which functions by inhibiting DNA gyrase.Target: DNA gyrase; AntibacterialNorfloxacin is a synthetic chemotherapeutic antibacterial agent occasionally used to treat common as well as complicated urinary tract infections. Norfloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, enzymes necessary to separate bacterial DNA, thereby inhibiting cell division.There are currently three approved uses in the adult population (one of which is restricted) and the other ineffective due to bacterial resistance. Chibroxin (ophthalmic) is approved for use in children older than one year of age.Norfloxacin is associated with a number of rare serious adverse reactions as well as spontaneous tendon ruptures and irreversible peripheral neuropathy. Tendon problems may manifest long after therapy had been completed and in severe cases may result in lifelong disabilities. Hepatoxicity resulting in fatalities has also been reported with the use of norfloxacin.
Benazepril, an angiotensin converting enzyme inhibitor, which is a medication used to treat high blood pressure.Target: angiotensin converting enzyme (ACE)Benazepril is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. Upon cleavage of its ester group by the liver, benazepril is converted into its active form benazeprilat, a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor [1].Animals were randomly divided into 4 groups: sham STNx group (control), STNx group, morning benazepril group (MB) and evening benazepril group (EB).Benazepril was intragastrically administered at a dose of 10 mg/kg/day at 07:00 and 19:00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light:dark cycle of 12:12 for 12 weeks. Systolic blood pressure (SBP), 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity (RA), angiotensin II (AngII) and aldosterone (Ald) by radioimmunoassay (RIA) and the mRNA expression profile of clock genes (bmal1, dbp and per2) by real-time PCR at 12 weeks. Our results showed that no significant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Ald and RA content of a day between the MB group and EB group. The expression peak of bmal1 mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects [2].Clinical indications: Congestive heart failure; End stage renal disease; HypertensionFDA Approved Date: Toxicity: headaches; cough; Anaphylaxis; angioedema; hyperkalemia
Isatin (Indoline-2,3-dione) is a potent inhibitor of monoamine oxidase (MAO) with an IC50 of 3 μM. Also binds to central benzodiazepine receptors (IC50 against clonazepam, 123 μM)[1]. Also acts as an antagonist of both atrial natriuretic peptide stimulated and nitric oxide-stimulated guanylate cyclase activity[2]. Shows effect on the serotonergic system[3].
Berbamine dihydrochloride is an inhibitor of NF-κB activity with remarkable anti-myeloma efficacy.
N-Nornuciferine is an aporphine alkaloid in lotus leaf that significantly inhibits CYP2D6 with IC50 and Ki of 3.76 and 2.34 μM, respectively.
Indole-3-carbinol suppresses NF-κB activity and also is an Aryl hydrocarbon receptor (AhR) agonist.
Epiberberine chloride, a natural alkaloid, is a BACE1 inhibitor, which also exhibits inhibition activity on CYP2D6 and aldose reductase, alpha-adrenoceptors, acetylcholinesterase (AChE), butyrylcholinesterase, and b-site amyloid precursor protein cleaving enzyme 1.