A new cyclopentylidene and other chemical constituents from Malaysian Crotalaria pallida

Crotalaria pallida Aiton is an herbaceous legume from the family Fabaceae. In the present study, one new cyclopentyliene, crotolidene (1) and seven known compounds, i.e. hydroxydihydrobovolide (2), octacosane (3), trans-phytyl palmitate (4), linoleic acid (5), methyl oleate (6), ethyl palmitate (7), and palmitic acid (8) were isolated from the C. pallida collected from Perak, Malaysia. These compounds were isolated and characterized using extensive chromatographic and spectroscopic methods

Isolation and identification of metabolites from the gram-negative Proteobacteria of Burkholderia cenocepacia and Serratia marcescens

Burkholderia cenocepacia and Serratia marcescens are Gram-negative proteobacteria commonly found in the natural environment and are also opportunistic pathogens that caused a number of human diseases. The fermentation culture of Burkholderia cenocepacia yielded three compounds, 4-(2-hydroxyethoxy)-phenol (1), Maculosin (2) and methyl myristate (3). Compound 2 was also isolated together with cyclo(L-Leu-L-Pro) (4) from Serratia marcescens. Compound 1 was isolated from a natural source for the first time and the first isolation of compounds 2-4 was also reported from both Burkholderia cenocepacia and Serratia marcescens

A new oxoaporphine and liriodenine’s anti-neuroblastoma potential from the roots of Polyalthia bullata King

Polyalthia bullata King’s root yielded a new compound named 5-methylliridine (1) in addition to six previously identified compounds. These known compounds include liriodenine (2), 11-methoxyliriodenine (3), lysicamine (4), onychine (5), 5-hydroxy-6-methoxyonychine (6), and 8-methoxyeupolauridine (7). The structures of compounds 1-7 were determined through spectroscopic analysis. Liriodenine (2) exhibited a remarkable ability to decrease the cell viability of cancerous N2A cells to 22% within a 24 h timeframe, indicating its potential as an anti-neuroblastoma agent. Molecular docking results additionally suggested that oxoaporphines (1-4) have the potential to act as inhibitors of protein kinases. These findings highlight the therapeutic potential of P. bullata constituents in cancer treatment, particularly neuroblastoma, and contribute to understanding its medicinal properties

Isolation and photophysical properties of Di- and Tri-substituted natural anthraquinones from Malaysian Morinda citrifolia

Five di- and tri-substituted natural anthraquinones, i.e. nordamnacanthal (1), damnacanthal (2), rubiadin (3), 1-methoxy-2-methyl-3-hydroxyanthraquinone (4) and 1-hydroxy-3-methoxyanthraquinone (5) were subjected to photophysical studies. The results indicated that steric hindrance and intramolecular hydrogen bonding are important factors that affect absorption and emission spectral of these natural anthraquinones. Besides that, emission properties were significantly enhanced with formation of intramolecular hydrogen bonding in 1,3-dihydroxy-2-aldehyde tri-substituted anthraquinone 1. This gave rise to formation of two additional quasi aromatic rings extending the π-conjugation system in the anthraquinone structure

Manzamine A reduces androgen receptor transcription and synthesis by blocking E2F8-DNA interactions and effectively inhibits prostate tumor growth in mice.

The androgen receptor (AR) is the main driver in the development of castration-resistant prostate cancer, where the emergence of AR splice variants leads to treatment-resistant disease. Through detailed molecular studies of the marine alkaloid manzamine A (MA), we identified transcription factor E2F8 as a previously unknown regulator of AR transcription that prevents AR synthesis in prostate cancer cells. MA significantly inhibited the growth of various prostate cancer cell lines and was highly effective in inhibiting xenograft tumor growth in mice without any pathophysiological perturbations in major organs. MA suppressed the full-length AR (AR-FL), its spliced variant AR-V7, and the AR-regulated prostate-specific antigen (PSA; also known as KLK3) and human kallikrein 2 (hK2; also known as KLK2) genes. RNA sequencing (RNA-seq) analysis and protein modeling studies revealed E2F8 interactions with DNA as a potential novel target of MA, suppressing AR transcription and its synthesis. This novel mechanism of blocking AR biogenesis via E2F8 may provide an opportunity to control therapy-resistant prostate cancer over the currently used AR antagonists designed to target different parts of the AR gene

Characterization of Quorum Sensing and Quorum Quenching Soil Bacteria Isolated from Malaysian Tropical Montane Forest

We report the production and degradation of quorum sensing N-acyl-homoserine lactones by bacteria isolated from Malaysian montane forest soil. Phylogenetic analysis indicated that these isolates clustered closely to the genera of Arthrobacter, Bacillus and Pseudomonas. Quorum quenching activity was detected in six isolates of these three genera by using a series of bioassays and rapid resolution liquid chromatography analysis. Biosensor screening and high resolution liquid chromatography-mass spectrometry analysis revealed the production of N-dodecanoyl-L-homoserine lactone (C12-HSL) by Pseudomonas frederiksbergensis (isolate BT9). In addition to degradation of a wide range of N-acyl-homoserine lactones, Arthrobacter and Pseudomonas spp. also degraded p-coumaroyl-homoserine lactone. To the best of our knowledge, this is the first documentation of Arthrobacter and Pseudomonas spp. capable of degrading p-coumaroyl-homoserine lactone and the production of C12-HSL by P. frederiksbergensis

Bisindole alkaloids

This chapter provides an overview on bisindole alkaloids. The indole–indole and tryptamine–tryptamine type, and related alkaloids are discussed. Tryptamine–tryptamine type with an additional monoterpene unit and related alkaloids are briefly discussed. Corynanthe–tryptamine is constituted from the union of a tryptamine unit and a corynanthe moiety. They are found mainly in plants of the genus Strychnos, but have also been isolated from other genera of the Apocynaceae, Rubiaceae, and Loganiaceae families. The bisindole alkaloid longicaudatine, first detected in various Strychnos species by its characteristic reaction with ferric chloride or Ce(IV) reagents, was obtained in a number of instances with its isomer, bisnorC-alkaloid H (284), which also showed the same chromatographic and chromogenic properties. Alstonia sphaerocapitata and A. undulata provided undulatine and deformylundulatine, respectively. The alkaloids are constituted from the union of a cabucraline unit and a N-methylpericyclivine unit, via C(10) of the former to C(6′) of the latter. The structures were elucidated on the basis of mass spectral and NMR data. The absolute configuration of vincristine is established by X-ray analysis of its methiodide derivative, from which the configurations of the stereocenters in vinblastine were inferred from the known relationship between the two compounds

Manzamine-A Alters In Vitro Calvarial Osteoblast Function

Manzamine-A is a marine-derived alkaloid which has anti-viral and anti-proliferative properties and is currently being investigated for its efficacy in the treatment of certain viruses (malaria, herpes, HIV-1) and cancers (breast, cervical, colorectal). Manzamine-A has been found to exert effects via modulation of SIX1 gene expression, a gene critical to craniofacial development via the WNT, NOTCH, and PI3K/AKT pathways. To date little work has focused on Manzamine-A and how its use may affect bone. We hypothesize that Manzamine-A, through SIX1, alters bone cell activity. Here, we assessed the effects of Manzamine-A on cells that are responsible for the generation of bone, pre-osteoblasts and osteoblasts. PCR, qrtPCR, MTS cell viability, Caspase 3/7, and functional assays were used to test the effects of Manzamine-A on these cells. Our data suggests Six1 is highly expressed in osteoblasts and their progenitors. Further, osteoblast progenitors and osteoblasts exhibit great sensitivity to Manzamine-A treatment exhibited by a significant decrease in cell viability, increase in cellular apoptosis, and decrease in alkaline phosphatase activity. In silico binding experiment showed that manzamine A potential as an inhibitor of cell proliferation and survival proteins, i.e., Iκb, JAK2, AKT, PKC, FAK, and Bcl-2. Overall, our data suggests Manzamine-A may have great effects on bone health overall and may disrupt skeletal development, homeostasis, and repair