New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, Thorectandra choanoides (CMB-01889).

Thorectandra choanoides (CMB-01889) was prioritized as a source of promising new chemistry from a library of 960 southern Australian marine sponge extracts, using a global natural products social (GNPS) molecular networking approach. The sponge was collected at a depth of 45 m. Chemical fractionation followed by detailed spectroscopic analysis led to the discovery of a new tryptophan-derived alkaloid, thorectandrin A (1), with the GNPS cluster revealing a halo of related alkaloids 1a-1n. In considering biosynthetic origins, we propose that Thorectandrachoanoides (CMB-01889) produces four well-known alkaloids, 6-bromo-1',8-dihydroaplysinopsin (2), 6-bromoaplysinopsin (3), aplysinopsin (4), and 1',8-dihydroaplysinopsin (10), all of which are susceptible to processing by a putative indoleamine 2,3-dioxygenase-like (IDO) enzyme to 1a-1n. Where the 1',8-dihydroalkaloids 2 and 10 are fully transformed to stable ring-opened thorectandrins 1 and 1a-1b, and 1h-1j, respectively, the conjugated precursors 3 and 4 are transformed to highly reactive Michael acceptors that during extraction and handling undergo complete transformation to artifacts 1c-1g, and 1k-1n, respectively. Knowledge of the susceptibility of aplysinopsins as substrates for IDOs, and the relative reactivity of Michael acceptor transformation products, informs our understanding of the pharmaceutical potential of this vintage marine pharmacophore. For example, the cancer tissue specificity of IDOs could be exploited for an immunotherapeutic response, with aplysinopsins transforming in situ to Michael acceptor thorectandrins, which covalently bind and inhibit the enzyme.

Dysidealactams and Dysidealactones: Sesquiterpene Glycinyl-Lactams, Imides, and Lactones from a Dysidea sp. Marine Sponge Collected in Southern Australia.

A GNPS molecular networking approach mapped a library of 960 southern Australian marine sponges and prioritized Dysidea sp. (CMB-01171) for chemical investigation. Although the published natural products literature on Australian Dysidea sponges extends back over half a century and suffers from the perception of being near exhausted, fractionation of Dysidea sp. (CMB-01171) led to the discovery of a family of 10 new biosynthetically and chemically related sesquiterpenes. Detailed spectroscopic analysis guided structure elucidation identified dysidealactams A-F (1-6), dysidealactones A and B (7 and 8), and two solvolysis artifacts, 9 and 10. The dysidealactams A-D (1-4) incorporate a rare glycinyl-lactam functionality, while dysidealactam E (5) is particularly noteworthy in incorporating an unprecedented glycinyl-imide moiety. In addition to expanding knowledge of Dysidea natural products, this study demonstrates the value of applying GNPS molecular networking to map chemical diversity and prioritize the selection of marine sponge extracts for more detailed chemical analysis.

Cacolides: Sesterterpene Butenolides from a Southern Australian Marine Sponge, Cacospongia sp.

Chemical analysis of a marine sponge, Cacospongia sp. (CMB-03404), obtained during deep sea commercial fishing activities off the southern coast of Australia, yielded an unprecedented family of sesterterpene α-methyl-γ-hydroxybutenolides, cacolides A⁻L (1⁻12), together with biosynthetically related norsesterterpene carboxylic acids, cacolic acids A⁻C (13⁻15). Structures were assigned on the basis of detailed spectroscopic analysis with comparisons to known natural products and biosynthetic considerations. In addition to revealing new chemical diversity, this study provided a valuable platform for comparing and contrasting the capabilities of the traditional dereplication technologies of HPLC-DAD, HPLC-MS and NMR, with those of the emerging HPLC-MS/MS approach known as global natural products social molecular networking (GNPS), as applied to marine sponge sesterterpene tetronic acids.

Evaluation of in vitro anti-inflammatory and antibacterial potential of Crescentia cujete leaves and stem bark.

BACKGROUND: The various parts of Cresecentia cujete have some important biological activities. In folklore medicine leaves are used to treat hematomas, tumors and hypertension. Fruit decoction is used to treat diarrhea, stomachaches, cold, bronchitis, cough, asthma, and urethritis. The present study was designed to explore the anti-inflammatory and antibacterial potential of C. cujete leaves and stem bark. Anti-inflammatory activity was evaluated by in vitro human red blood cell (HRBC) membrane stabilization method and antibacterial activity by disc diffusion method. METHODS: In vitro anti-inflammatory activity was evaluated by human red blood cell (HRBC) membrane stabilization method while in vitro antibacterial activity was evaluated using cultures of Escherichia coli and Staphylococcus aureus by disc diffusion method. Total phenolic (TPC) and total flavonoid contents (TFC) of the crude extract and fractions were also determined by Folin-Ciocalteu's phenol reagent and by aluminium chloride method, respectively. RESULTS: The crude ethanol extract (CEE) of leaves and bark (concentration of each 1.0 mg/ml) demonstrated strong membrane stabilizing activity (53.86 and 61.85% protection, respectively), whereas their chloroform fractions (CHF) revealed moderate activity (48.74 ± 0.56 and 43.55 ± 6.20 %, respectively) compared with standard aspirin (concentration 0.10 mg/ml) which showed 75.81% protection in this test. All the samples showed a dose dependent anti-inflammatory activity in HRBC membrane stabilization test. Total phenolic (TPC) and total flavonoid contents (TFC) of the crude extract and fractions were also determined. Again, in in vitro antibacterial study, the extractives exhibited potent antibacterial activity. CONCLUSION: Results from this study showed that the leaves and bark of C. cujete possessed anti-inflammatory as well as antibacterial activities indicating that the plant extract has therapeutic potential against the bacterial infection and also have effect on disease processes by causing destabilization of biological membranes.

Comparative study of antidiabetic activity of Cajanus cajan and Tamarindus indica in alloxan-induced diabetic mice with a reference to in vitro antioxidant activity.

BACKGROUND: Oxidative stress not only develops complications in diabetic (type 1 and type 2) but also contributes to beta cell destruction in type 2 diabetes in insulin resistance hyperglycemia. Glucose control plays an important role in the pro-oxidant/antioxidant balance. Some antidiabetic agents may by themselves have antioxidant properties independently of their role on glucose control. OBJECTIVE: The present investigation draws a comparison of the protective antioxidant activity, total phenol content and the antihyperglycemic activity of the methanolic extract of Cajanus cajan root (MCC) and Tamarindus indica seeds (MTI). MATERIALS AND METHODS: Antidiabetic potentials of the plant extracts were evaluated in alloxan-induced diabetic Swiss albino mice. The plant extracts at the doses of 200 and 400 mg/kg body weight was orally administered for glucose tolerance test during 1-hour study and hypoglycemic effect during 5-day study period in comparison with reference drug Metformin HCl (50 mg/kg). In vitro antioxidant potential of MCC and MTI was investigated by using 1, 1- diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity at 517 nm. Total phenolic content, total antioxidant capacity and reducing power activity was also assayed. RESULTS: There was a significant decrease in fasting serum glucose level (P < 0.001), reduction in blood glucose level (P < 0.001) in 5-days study, observed in the alloxan-induced diabetic mice. The reduction efficacy of blood glucose level of both the extracts is proportional to their dose but MCC is more potent than MTI. Antioxidant study and quantification of phenolic compound of both the extracts revealed that they have high antioxidant capacity. CONCLUSION: These studies showed that MCC and MTI have both hypoglycemic and antioxidant potential but MCC is more potent than MTI. The present study suggests that both MCC and MTI could be used in managing oxidative stress.

Anti-nociceptive and anti-inflammatory activities of Wrightia arborea.

Anti-nociceptive and anti-inflammatory effects of methanolic extract of Wrightia arborea (MEWA) were examined using different models in rats. MEWA was given to rats orally upto 2000 mg kg(-1) b.wt. for acute toxicity study and observed for 14 days. Anti-nociceptive activity was evaluated in rats against Acetic acid induced writhing (chemically induced pain) and Tail immersion method (thermally induced pain). Acute anti-inflammatory activity of MEWA was also evaluated in Formaline-induced rat paw edema model and Carrageenan-induced hind paw edema model in rats. Results demonstrated that no mortality was found upto single dose of 2000 mg kg(-1) b.wt. in rats even after 14 days observation. In comparison to control group MEWA at 100 and 200 mg kg(-1) b.wt. showed highly significant anti-nociceptive activity against chemically (p < 0.001) as well as thermally (p < 0.05 and p < 0.001) induced pain as compared to standard drugs, indomethacin and nalbufin, respectively. In the formalin test, both the doses of 100 and 200 mg kg(-1) of extract significantly prevented increase in volume of paw edema (p < 0.05 and p < 0.01) both in the neurogenic and inflammatory phases. MEWA (200 and 400 mg kg(-1) p.o.) also significantly prevented increase in volume of paw edema in Carrageenan test (p < 0.05 and p < 0.001). The results suggest that MEWA has significant analgesic and anti-inflammatory potential which may be mediated by central and peripheral mechanism.

Antinociceptive and anti-inflammatory activities of flower (Alangium salvifolium) extract.

The present study aimed to evaluate the antinociceptive and anti-inflammatory activity of Alangium salvifolium (AS) flower in mice. The antinociceptive activity was determined using tail immerson, acetic acid induced writhing and formalin induced licking test. Antiinflammatory effects were evaluated using carrageenan and formalin induced paw edema in mice. The methanol extract (50 and 100 mg kg(-1)) of flower of AS followed by chloroform extract (100 mg kg(-1)) produced a significant inhibition of both phases of the formalin pain test in mice, a reduction in mice writhing induced by acetic acid and delayed the response of mice to hot water thermal stimulation in tail immersion test. All flowers extract of AS also produced a substantial inhibition (nearly 50%) of carrageenan and formalin induced paw edema. The inhibitions were similar to those produced by indomethacin, p.o. The different alkaloids and flavonoids found in the extract could be account for the antinociceptive and anti-inflammatory actions.