Isolaureline

Natural Aporphine Alkaloids with Potential to Impact Metabolic Syndrome.[Pubmed:34684698]

Molecules. 2021 Oct 10;26(20):6117.

The incidence and prevalence of metabolic syndrome has steadily increased worldwide. As a major risk factor for various diseases, metabolic syndrome has come into focus in recent years. Some natural aporphine alkaloids are very promising agents in the prevention and treatment of metabolic syndrome and its components because of their wide variety of biological activities. These natural aporphine alkaloids have protective effects on the different risk factors characterizing metabolic syndrome. In this review, we highlight the activities of bioactive aporphine alkaloids: thaliporphine, boldine, nuciferine, pronuciferine, roemerine, dicentrine, magnoflorine, anonaine, apomorphine, glaucine, predicentrine, Isolaureline, xylopine, methylbulbocapnine, and crebanine. We particularly focused on their impact on metabolic syndrome and its components, including insulin resistance and type 2 diabetes mellitus, endothelial dysfunction, hypertension and cardiovascular disease, hyperlipidemia and obesity, non-alcoholic fatty liver disease, hyperuricemia and kidney damage, erectile dysfunction, central nervous system-related disorder, and intestinal microbiota dysbiosis. We also discussed the potential mechanisms of actions by aporphine alkaloids in metabolic syndrome.

Involvement of fat mass and obesity gene (FTO) in the anti-obesity action of Annona muricata Annonaceae: in silico and in vivo studies.[Pubmed:32420297]

J Diabetes Metab Disord. 2020 Mar 12;19(1):197-204.

BACKGROUND: Annona muricata (Annonaceae) known as soursop is a common tropical plant species known for its numerous medicinal properties including obesity. The underlying mechanism of anti-obesity effect of A. muricata was investigated. The fat mass and obesity associated protein (FTO) is a validated potential target for anti-obesity drugs. METHODS: The interaction of compounds previously characterized from A. muricata was investigated against FTO using Autodock Vina. Also, modulation of FTO and STAT-3 mRNA expression by A. muricata was investigated in high fat diet induced obese rats (HFDR) using RT-PCR. RESULTS: A significant up-regulation of FTO gene was observed in HFDR when compared to control rats, while administration of A. muricata (200 mg/kg) significantly (p < 0.05) down-regulated FTO gene expression when compared to HFDR group. The effect of obesity on STAT-3 gene expression was also reversed by A. muricata (200 mg/kg). In silico study revealed annonaine and annonioside (-9.2 kcal/mol) exhibited the highest binding affinity with FTO, followed by anonaine and Isolaureline (-8.6 kcal/mol). Arg-96 is a critical amino acid enhancing anonaine, Isolaureline-FTO binding. CONCLUSION: This study suggests the possible anti-obesity mechanism of A. muricata is via down-regulation of FTO with concomitant up-regulation of STAT-3 genes. This study confirmed the use of this plant in the management of obesity and the probable compounds responsible for its antiobesity effect are annonaine and annonioside.

In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT(2) and alpha(1) receptors.[Pubmed:30216681]

Chem Biol Drug Des. 2019 Feb;93(2):132-138.

Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT(2) and alpha(1) adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5-HT(2) and adrenergic alpha(1) receptor subtypes were evaluated. The enantiomers of Isolaureline and dicentrine acted as antagonists at 5-HT(2) and alpha(1) receptors with (R)-Isolaureline showing the greatest potency (pK(b) = 8.14 at the 5-HT(2C) receptor). Both (R)- and (S)-glaucine also antagonized alpha(1) receptors, but they behaved very differently to the other compounds at 5-HT(2) receptors: (S)-glaucine acted as a partial agonist at all three 5-HT(2) receptor subtypes, whereas (R)-glaucine appeared to act as a positive allosteric modulator at the 5-HT(2A) receptor.

Revealing the potency of Annona muricata leaves extract as FOXO1 inhibitor for diabetes mellitus treatment through computational study.[Pubmed:28653156]

In Silico Pharmacol. 2016 Dec;5(1):3.

FOXO1 protein inactivation in the nucleus is one of targets for the treatment of diabetes mellitus. Annona muricata leaves contain flavonoid and phenolic compound alkaloids that were known to be able to increase pancreatic beta cell proliferation in animal experiment. This research aimed to predict the active compound ability of the Annona muricata leaves to bind and inhibit FOXO1 protein through in silico study. Analysis of molecular docking was performed by using Autodock Vina PyRx. this research proved that anonaine, rutin, muricatocin a, Isolaureline, xylopine, and kaempferol 3-O-rutinoside had an equal or smaller free binding energy compared to the control compound. Rutin and Muricatocin A had the same binding ability toward 66% amino acid residues, compared to control compound with hydrogen bond type, while xylopine, anonaine, Isolaureline, kaempferol 3-O-rutinoside had a similar binding ability towards 33% amino acid residues compared to control compound with hydrogen bond type.

Anti cancer activity on Graviola, an exciting medicinal plant extract vs various cancer cell lines and a detailed computational study on its potent anti-cancerous leads.[Pubmed:23889049]

Curr Top Med Chem. 2013;13(14):1666-73.

Nature is the world's best chemist: Many naturally occurring compounds have very complicated structures that present great challenges to chemists wishing to determine their structures or replicate them. The plant derived herbal compounds have a long history of clinical use, better patient tolerance and acceptance. Their high ligand binding affinity to the target introduce the prospect of their use in chemo preventive applications; in addition they are freely available natural compounds that can be safely used to prevent various ailments. Plants became the basis of traditional medicine system throughout the world for thousands of years and continue to provide mankind with new remedies. Here, we present a research study on a medicinal plant, Graviola, a native of North America but rarely grown in India. It has a wide potent anticancerous agents coined as Acetogenins which play a key role towards many varieties of cancer, Acetogenins are potent inhibitors of NADH oxidase of the plasma membranes of cancer cells. Potent leads were taken for the study through literature survey, major types of cancer targets were identified, the natureceuticals and the cancer protein were subjected to docking analysis, further with the help of the dock score and other descriptor properties top ranked molecules were collected, commercial drug was also selected and identified as a Test compound for the study. Later, the phytochemicals were subjected to toxicity analysis. Those screened compounds were then considered for active site analysis and to find the best binding site for the study. R Programming library was used to find the best leads. Phytochemicals such as Anonaine, Friedelin, Isolaureline, Annonamine, Anomurine, Kaempferol, Asimilobine, Quercetin, Xylopine were clustered and the highly clustered compounds such as Annonamine , Kaempferol termed to be a potential lead for the study. Further study on experimental analysis may prove the potentiality of these compounds. In the experimental analysis, Graviola leaves were collected, and the extracted components were tested against the HeLa cell line and PC3 cell line. HeLa cells treated with 75 mug of a crude leaf extract of A. muricata showing 80% of cell inhibition. Further investigation of other experimental studies may confirm that these potential lead could make a great impact in which it could help to accelerate the pipeline of drug discovery.