Phytochemical Investigation of Psychoactive Medicinal Plants for the Treatment of Neurological Disorders

Neurological disorders include disorders such as migraine, tension-type headaches, Parkinson’s disease (PD), epilepsy, dementia, and Alzheimer’s disease (AD). Globally, PD is the second most comneurodegenerative disorder following AD. In developed countries, PD affects 1% of all population over 60 years of age. The prevalence of PD is increasing over the years and is expected to double by 2030. It is proposed that combination of dopaminergic drugs with monoamine oxidase B (MAO-B) inhibitors, anticholinergics, catechol-O-methyl transferase inhibitors, and other non-dopaminergic drugs can better alleviate levodopa-induced motor complications along with better control of motor symptoms. MAO-B inhibitors play a significant role in dopamine (DA) metabolism and can be used as monotherapy in the early stages of PD, or in combination with levodopa. Currently, there are only three MAO-B inhibitors that are approved by Food and Drug Administration (FDA): selegiline, rasagiline, and safinamide. Hence, there is the need to discover potent and selective MAO-B inhibitors for effective treatment of PD. About 60% of the marketed drugs today are either natural products or derivatives that are inspired from natural products. We studied plants with extensive traditional use in CNS-related disorders, in which the chloroform extract of C. urticifolia exhibited potent inhibition of MAO-A and -B. Calea urticifolia (Asteraceae) commonly known as “Juanislama” is native to the Central America. Bioassay-guided fractionation has been implemented for the isolation of the secondary metabolites from C. urticifolia. From the bioactive fraction, acacetin and a series of sesquiterpenes were isolated; acacetin was found to be the bioactive compound. A series of acacetin analogs were designed with the aid of computational docking studies, to improve their selectivity towards MAO-B. The structures of the isolated compounds were determined on the basis of HR-MS and 1D- and 2D-NMR studies; configurations were partly established by ECD calculations. Monoamine oxidase assays were performed on the extracts, fractions, and purified compounds. Molecular modeling and molecular dynamic studies were used to predict the binding modes on the active sites of the MAO isoenzymes

Computationally assisted lead optimization of novel potent and selective mao-b inhibitors

A series of dietary flavonoid acacetin 7-O-methyl ether derivatives were computationally designed aiming to improve the selectivity and potency profiles against monoamine oxidase (MAO) B. The designed compounds were evaluated for their potential to inhibit human MAO-A and-B. Compounds 1c, 2c, 3c, and 4c were the most potent with a Ki of 37 to 68 nM against MAO-B. Compounds 1c–4c displayed more than a thousand-fold selectivity index towards MAO-B compared with MAO-A. Moreover, compounds 1c and 2c showed reversible inhibition of MAO-B. These results provide a basis for further studies on the potential application of these modified flavonoids for the treatment of Parkinson’s Disease and other neurological disorders

Monanchocidin A From Subarctic Sponges of the Genus Monanchora and Their Promising Selectivity Against Melanoma in vitro

© Copyright © 2020 Gogineni, Oh, Waters, Kelly, Stone and Hamann. Marine sources have long been known for their potential to produce unique skeletons and various biological activities. Fractionation of the ethanol extracts of an undescribed species of Monanchora Carter, 1883 and a specimen closely comparable to Monanchora pulchra (Lambe, 1894/1895) (Class Demospongiae, Order Poecilosclerida, Family Crambeidae), yielded a known compound, monanchocidin A. Monanchocidin A, a secondary metabolite, showed very modest antibacterial, antifungal, and antiprotozoal activities with IC50 values ranging between 255.75 and 7288.92 μM. Monanchocidin A also exhibited potent selective activity for the melanoma panel in the NCI cancer cell screening panel

Perspective on the Therapeutics of Anti-Snake Venom

Snakebite envenomation is a life-threatening disease that was recently re-included as a neglected tropical disease (NTD), affecting millions of people in tropical and subtropical areas of the world. Improvement in the therapeutic approaches to envenomation is required to palliate the morbidity and mortality effects of this NTD. The specific therapeutic treatment for this NTD uses snake antivenom immunoglobulins. Unfortunately, access to these vital drugs is limited, principally due to their cost. Different ethnic groups in the affected regions have achieved notable success in treatment for centuries using natural sources, especially plants, to mitigate the effects of snake envenomation. The ethnopharmacological approach is essential to identify the potential metabolites or derivatives needed to treat this important NTD. Here, the authors describe specific therapeutic snakebite envenomation treatments and conduct a review on different strategies to identify the potential agents that can mitigate the effects of the venoms. The study also covers an increased number of literature reports on the ability of natural sources, particularly plants, to treat snakebites, along with their mechanisms, drawbacks and future perspectives

Role of Marine Natural Products in the Genesis of Antiviral Agents

Role of Marine Natural Products in the Genesis of Antiviral Agent

Computationally Assisted Lead Optimization of Novel Potent and Selective MAO-B Inhibitors

A series of dietary flavonoid acacetin 7-O-methyl ether derivatives were computationally designed aiming to improve the selectivity and potency profiles against monoamine oxidase (MAO) B. The designed compounds were evaluated for their potential to inhibit human MAO-A and -B. Compounds 1c, 2c, 3c, and 4c were the most potent with a Ki of 37 to 68 nM against MAO-B. Compounds 1c–4c displayed more than a thousand-fold selectivity index towards MAO-B compared with MAO-A. Moreover, compounds 1c and 2c showed reversible inhibition of MAO-B. These results provide a basis for further studies on the potential application of these modified flavonoids for the treatment of Parkinson’s Disease and other neurological disorders

Isolation of Acacetin from <i>Calea urticifolia</i> with Inhibitory Properties against Human Monoamine Oxidase‑A and -B

<i>Calea urticifolia</i> (Asteraceae: Asteroideae) has long been used as a traditional medicine in El Salvador to treat arthritis and fever, among other illnesses. The chloroform extract of the leaves of <i>C. urticifolia</i> showed potent inhibition of recombinant human monoamine oxidases (MAO-A and -B). Further bioassay-guided fractionation led to the isolation of a flavonoid, acacetin, as the most prominent MAO inhibitory constituent, with IC₅₀ values of 121 and 49 nM for MAO-A and -B, respectively. The potency of MAO inhibition by acacetin was >5-fold higher for MAO-A (0.121 μM vs 0.640 μM) and >22-fold higher for MAO-B (0.049 μM vs 1.12 μM) as compared to apigenin, the closest flavone structural analogue. Interaction and binding characteristics of acacetin with MAO-A and -B were determined by enzyme-kinetic assays, enzyme–inhibitor complex binding, equilibrium–dialysis dissociation analyses, and computation analysis. Follow-up studies showed reversible binding of acacetin with human MAO-A and -B, resulting in competitive inhibition. Acacetin showed more preference toward MAO-B than to MAO-A, suggesting its potential for eliciting selective pharmacological effects that might be useful in the treatment of neurological and psychiatric disorders. In addition, the binding modes of acacetin at the enzymatic site of MAO-A and -B were predicted through molecular modeling algorithms, illustrating the high importance of ligand interaction with negative and positive free energy regions of the enzyme active site