A new labdane diterpenoid, in vitro and in silico cytotoxicity, and protease inhibitory effects of phytochemicals from Juniperus polycarposK. Koch leaves.

Cytotoxicity-guided purification of Juniperus polycarpos K. Koch leaves (Cupressaceae) led to the isolation of a new labdane diterpenoid, 3-(acetyloxy)-acetylisocupressic acid (1), together with isocupressic acid (2), 3,4-dimethoxycinnamoyl alcohol (3) and deoxypodophyllotoxin (4). The chemical structures of 1-4 were established by detailed 1D and 2D NMR, HRFAB-MS and LRESI-MS, as well as by comparing the spectral data with those reported in the literature. Compound 1 was ineffective against HepG2 cells and protease enzyme, while 2 showed potent cytotoxicity against HepG2 cells (IC50 of 3.73 µg/mL) compared to cisplatin (IC50 of 12.65 µg/mL). Computational analyses with CDK1 protein (a prominent protein in the cell cycle of HepG2 cells) revealed the binding affinity of 2 (-31.86 kcal/mol) was better than 1 (-19.70 kcal/mol) because the acetoxy groups did not allow binding deeply to the ATP binding site. Compounds 2 and 4 moderately inhibited the protease activity (IC50 = 52.7 and 63.0 µg/mL, respectively). Further in vitro and in vivo studies on the plant are strongly recommended.

In Vitro and In Vivo Antidiabetic, α-Glucosidase Inhibition and Antibacterial Activities of Three Brown Algae, Polycladia myrica, Padina antillarum, and Sargassum boveanum, and a Red Alga, Palisada perforata from the Persian Gulf.

Background: In recent decades, algae have attracted worldwide attention for their great biological activities, such as antidiabetic and antibacterial properties. Objectives: We measured antibacterial and α-glucosidase inhibition potential of methanol and 80% methanol extracts of three brown algae species, Polycladia myrica, Padina antillarum, and Sargassum boveanum, and a red alga, Palisada perforata, from the Persian Gulf coasts. Methods: Antibacterial activity of the algal extracts was assessed by broth dilution method against three gram-negative and -positive bacteria, including Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa; Staphylococcus epidermidis, Staphylococcus aureus, and Bacillus subtilis, respectively. Furthermore, the yeast's α-glucosidase inhibition of the algal extracts was measured via colorimetric assay. In addition, we investigated the beneficial effect of 80% MeOH extract of S. boveanum on the blood glucose levels in streptozotocin-induced diabetic rats. Results: The MeOH extract of S. boveanum was the best antibacterial extract with MIC = 2.5 mg/mL against all bacterial strains except for E. coli. The MeOH and 80% MeOH extracts of P. myrica and P. antillarum inhibited α-glucosidase at most with IC50 values of 12.70 ± 1.88 µg/mL and 13.06 ± 4.44 µg/mL, respectively. The oral gavage of S. boveanum extract in streptozotocin- (STZ-) induced diabetic rats resulted in decreasing their postprandial blood glucose levels. The algae and acarbose decreased blood glucose levels after sucrose administration in 60 minutes, compared to the non-drug-treated animals, with p values of 0.03 and 0.007, respectively. Conclusions: Overall, due to the in vitro and in vivo antidiabetic potential of S. boveanum, we suggest the alga as a new source for the isolation and identification of potential antidiabetic and antibacterial compounds.

Comparison of inhibitory activities of 50 Salvia species against α-Glucosidase.

Objectives: Type 2 diabetes is a common metabolic disease affecting millions of people worldwide. α-Glucosidase inhibitors can be used as one of the therapeutic approaches to decrease the postprandial glucose levels through the inhibition of carbohydrate hydrolysis. Medicinal plants are one of the main sources of α-glucosidase's natural inhibitors. In this study, we report the inhibitory effects of 50 different accessions of 32 Salvia species against α-glucosidase. Methods: To estimate the relative potency of the crude extracts, the inhibitory activities of the 80% methanol of the plants extracts were determined in three different concentrations (1000, 500 and 250 µg/ml) and compared to that of acarbose as the positive control. Results: S. multicaulis, S. santolinifolia, S. dracocephaloides, and S. eremophila were stronger inhibitors than acarbose (p < 0.05) with IC50 values in the range of 26.23- 92.35 µg/mL. According to the LC-PDA-ESIMS and NMR analysis of crude extracts of the studied Salvia species, 8 phytochemicals including luteolin-7-O-glucoside (1) luteolin-7-O-glucuronide (2), apigenin-7-O-glucoside (3), apigenin-7-O-glucuronide (4), Hispidulin-7-O-glucuronide (5), hispidulin-7-O-glucoside (6), rosmarinic acid (7), carnosol (8) and carnosic acid (9) were identified as the most common α-glucosidase inhibitors. The above compounds constituted the major compounds in the active Salvia species in the range of 1.5-95.0%. Among them rosmarinic acid (39-95%) was detected in almost all potent α -glucosidase inhibitor species. Therefore, it can be considered as a biochemical marker in the antidiabetic Salvia species in addition to the other minor compounds. Conclusions: Considering the high α-glucosidase inhibitory potential of the four- out of fifty Salvia species, they are suggested for further in vivo antidiabetic tests as potential medicinal plants.

The correlation among residual nitrites, biogenic amines, N-nitrosamine formation, and degradation occurrence of punicalagin α/ß, rosmarinic acid, carnosol, and carnosic acid in extract-treated sausage during storage.

The aim of this study was to investigate the relation between residual α- and ß-punicalagin in Punica granatum L.; PPE and rosmarinic acid, carnosol, and carnosic acid in Salvia eremophila (SE) with residual nitrites, biogenic amines (cadaverine, putrescine, and histamine), N-nitrosodimethylamine (NDMA), microbial counts, lipid oxidation indices, and color values in extract-treated sausage over 14 days of storage. Sausage containing SE + nitrite 60 ppm (SSN) showed minimum levels of the residual nitrites (13.14 mg/kg), NDMA (0.74 ± 0.05 µg/kg), and biogenic amine (histamine, 1.8 mg/kg; cadaverine, 3.7 mg/kg; and putrescine, 4.3 mg/kg) due to retarded degradation rate of 285.84-216.44 mg/kg; rosmarinic acid, 41.62-33.16 mg/kg; carnosol, and 88.70-76.73 mg/kg; carnosic acid over storage time. The first-order kinetic model fitted well for the degradation of rosmarinic acid and carnosol acid in SSN sample. TBA value remained below the threshold limit (0.32 mg kg-1) through 14 days for SSN. Second-order and zero-order reaction models had the best agreement with sausages' PV and TBA values, respectively. After 2 weeks of storage, E. coli and Cl. perfringens counts in the SN120 (sausage containing 120 ppm nitrite) and SSN were significantly lower than the other samples (p < .05), with the values 2.1 and 1.5 log cfu/g for SN120 and 2.2 and 1.6 log cfu/g for SSN formulation. Conversely, oxidation indices, residual nitrites, NDMA, and biogenic amine increased in sausage samples containing PPE extracts (SPN) owing to total degradation of α- and ß-punicalagin during storage. The results indicated that SE can be used as potential co-preservative by reducing the levels of required nitrite in food industry.

Neuropharmacological Potential of Diterpenoid Alkaloids.

This study provides a narrative review of diterpenoid alkaloids (DAs), a family of extremely important natural products found predominantly in some species of Aconitum and Delphinium (Ranunculaceae). DAs have long been a focus of research attention due to their numerous intricate structures and diverse biological activities, especially in the central nervous system (CNS). These alkaloids originate through the amination reaction of tetra or pentacyclic diterpenoids, which are classified into three categories and 46 types based on the number of carbon atoms in the backbone structure and structural differences. The main chemical characteristics of DAs are their heterocyclic systems containing ß-aminoethanol, methylamine, or ethylamine functionality. Although the role of tertiary nitrogen in ring A and the polycyclic complex structure are of great importance in drug-receptor affinity, in silico studies have emphasized the role of certain sidechains in C13, C14, and C8. DAs showed antiepileptic effects in preclinical studies mostly through Na+ channels. Aconitine (1) and 3-acetyl aconitine (2) can desensitize Na+ channels after persistent activation. Lappaconitine (3), N-deacetyllapaconitine (4), 6-benzoylheteratisine (5), and 1-benzoylnapelline (6) deactivate these channels. Methyllycaconitine (16), mainly found in Delphinium species, possesses an extreme affinity for the binding sites of α7 nicotinic acetylcholine receptors (nAChR) and contributes to a wide range of neurologic functions and the release of neurotransmitters. Several DAs such as bulleyaconitine A (17), (3), and mesaconitine (8) from Aconitum species have a drastic analgesic effect. Among them, compound 17 has been used in China for decades. Their effect is explained by increasing the release of dynorphin A, activating the inhibitory noradrenergic neurons in the ß-adrenergic system, and preventing the transmission of pain messages by inactivating the Na+ channels that have been stressed. Acetylcholinesterase inhibitory, neuroprotective, antidepressant, and anxiolytic activities are other CNS effects that have been investigated for certain DAs. However, despite various CNS effects, recent advances in developing new drugs from DAs were insignificant due to their neurotoxicity.

Inhibitory Potential of Six Brown Algae from the Persian Gulf on α-Glucosidase and In Vivo Antidiabetic Effect of Sirophysalis Trinodis.

Background: Brown algae have gained worldwide attention due to their significant biological activities, such as antidiabetic properties. In the present study, the antidiabetic properties of six brown algae from the Persian Gulf were investigated. Methods: An experimental study was conducted from 2017 to 2019 to examine the inhibitory effects of six brown algae against the α-glucosidase activity. Methanol (MeOH) and 80% MeOH extracts of Colpomenia sinuosa, Sargassum acinaciforme, Iyengaria stellata, Sirophysalis trinodis, and two accessions of Polycladia myrica were analyzed. The effect of 80% MeOH extracts of Sirophysalis trinodis on blood glucose levels in streptozotocin-induced diabetic rats was evaluated. Chemical constituents of brown algae were analyzed using thin-layer chromatography and liquid chromatography-mass spectrometry techniques. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant. Results: The 80% MeOH extracts of Iyengaria stellata (IC50=0.33±0.15 µg/mL) and Colpomenia sinuosa (IC50=3.50±0.75 µg/mL) as well as the MeOH extracts of Colpomenia sinuosa (IC50=3.31±0.44 µg/mL) exhibited stronger inhibitory effect on α-glucosidase than the acarbose (IC50=160.15±27.52 µg/mL, P<0.001). The 80% MeOH extracts of Sirophysalis trinodis reduced postprandial blood glucose levels in diabetic rats compared to the control group (P=0.037). Fucoxanthin was characterized as the major antidiabetic agent in most of the algal extracts. Conclusion: Sirophysalis trinodis is recommended as a novel source for isolation and identification of potential antidiabetic compounds due to its high in vivo and in vitro antidiabetic effects.

Anti-COVID-19 and antidiabetic activities of new oleanane and ursane-type triterpenoids from Salvia grossheimii: an in-silico approach.

Salvia grossheimii is a perennial herb with antidiabetic and cytotoxic constituents. In continuation of our study on S. grosshiemii to identify the bioactive phytochemicals, we have reported the characterization of seven undescribed triterpenoids. The aerial parts of the plant were extracted in dichloromethane and its constituents were isolated using chromatography techniques. The structures of compounds were identified using 1D, 2D NMR, and ESI-MS spectral data. Seven new oleanane- and ursane-type triterpenoids (1-7) were identified in S. grossheimii. The structures of 1-7 were characterized as; 2α-hydroxy-3ß-acetoxy-olean-9(11),12-diene (1), 2α-acetoxy-3ß-hydroxy-olean-9(11),12-diene (2), 3ß-acetoxy-olean-18-ene,2α,11α-diol (3), 2α-hydroxy-3ß-acetoxy-urs-9(11),12-diene (4), 2α-acetoxy-3ß-hydroxy-urs-9(11),12-diene (5), 2α,3ß-diacetoxy-urs-12-ene-11α,20ß-diol (6), 2α,3ß-diacetoxy-urs-9(11),12-diene-20ß-ol (7). Triterpenoids (2, 5, and 7) were intramolecular transesterification or dehydration products of their corresponding isomers or allylic alcohol in the C rings, respectively, produced in-situ during NMR spectroscopy. Virtual screening of 1-7 was performed with molecular docking analysis to identify the potential SARS-CoV-2 and α-glucosidase inhibitors using the smina molecular docking algorithm. The best binding energy values (kcal/mol) against COVID-19 main protease Mpro were calculated for 6 (-8.77) and 7 (-8.68), and the higher binding affinities toward human α-glucosidase were obtained for 2 (-9.39) and 6 (-8.63). This study suggests S. grossheimii as a rich source of bioactive triterpenoids and introduces new natural compounds. Considering the high binding energy values of 2, 6, and 7, these structures could be candidates for anti-COVID-19 and antidiabetic drug development in the future.

Phytochemical Analysis and Biological Activity of Salvia compressa Vent.

Background: Salvia extracts have various biological activities and are rich sources of bioactive metabolites. Objectives: We identified five phytochemicals from S. compressa extract and assessed its biological properties. Methods: The plant's shoots were extracted using dichloromethane, and the constituents were isolated using column chromatography. High-resolution NMR spectroscopy characterized the chemical structures of the compounds (1 - 5). The cytotoxic effect of the extract was examined against MCF-7 cells by MTT reduction assay, while cisplatin was tested as a reference cytotoxic compound. The antibacterial activity was assessed using nutrient broth micro-dilution (NBMD), and chloramphenicol was used as the positive control. Results: Citrostadienol (1), ß-sitosterol (2), two glyceride esters of linolenic, linoleic, and palmitic acids (3, 4), and geraniol (5) were isolated from S. compressa for the first time. The extract showed activity against MCF-7 breast cancer cells and reduced cell viability to 68.2 ± 13.1% compared to the control drug at the concentration of 50 µg/mL, while it was not active against seven test bacteria. Conclusions: The anti-complementary activity of the isolated steroids suggests S. compressa for future anti-inflammatory research.

Cytotoxic abietane-type diterpenoids from roots of Salvia spinosa and their in Silico pharmacophore modeling.

The roots of Salvia spinosa L. (Lamiaceae) were extracted with hexane, dichloromethane (DCM) and ethyl acetate. The DCM extract exhibited cytotoxic activity (IC50 32.7 µg/mL) against MFC-7 breast cancer cell line in MTT colorimetric bioassay. Ferruginol (1), taxodione (2), 12-deoxy-6-hydroxy-6,7-dehydroroyleanone (3), 14-deoxycoleon U (4), 15-deoxyfuerstione (5) and taxodone (6) were isolated from the DCM roots extract. Their structures were elucidated by a combination of spectroscopic analyses including EIMS and 1H- and 13C NMR spectra. The cytotoxicity of compound 3 was determined against MCF-7 and K562 cell lines and compared with the other compounds. A pharmacophore model was built based on potent input compounds to resolve important pharmacophore features responsible for cytotoxic activity of the isolated compounds.

Two new cytotoxic ursane triterpenoids from the aerial parts of Salvia urmiensis Bunge.

Bioassay-guided fractionation of a dichloromethane extract of the aerial parts of Salvia urmiensis, an endemic plant species of Iran, led to the isolation of two new cytotoxic ursane triterpenoids, Salvurmin A and Salvurmin B. Their structures were elucidated by a combination of 1D and 2D NMR, HR-ESI-MS, IR and UV analysis. Cytotoxicity of the above-mentioned compounds were evaluated against two human cancerous cell lines (SW1116, MCF-7). IC50 values for Salvurmin A and Salvurmin B on colon cancer cell line (SW1116) were 41.6 ± 2.6 and 23.2 ± 0.4 µM respectively, in comparison to cisplatin as control positive. In addition, these two compounds exhibited cytotoxic activity on breast cancer cell line (MCF-7) with an IC50 of 54.2 ± 5.3 and 40.2 ± 3.1 µM for Salvurmin A and Salvurmin B, respectively. The cytotoxic activities of these two compounds present a promising potential for the future investigation on this endemic species of Salvia.

Cytotoxic furanosesquiterpenoids and steroids from Ircinia mutans sponges.

CONTEXT: Ircinia mutans Wilson (Irciniidae) is a sponge with antimicrobial and cytotoxic constituents. OBJECTIVE: Our objective was to characterise the cytotoxic constituents of two seasonal collections of I. mutans. MATERIALS AND METHODS: The sponges were extracted in methanol-dichloromethane and their constituents were purified and characterised using column chromatography, GC-MS, 1 D and 2 D NMR. Anti-proliferative activities of the compounds, were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay (0.25-100 µg/mL, 72 h) against leukaemia (MOLT-4), breast (MCF-7) and colon cancer (HT-29) human cells. RESULTS: Three furanosesquiterpoids; furodysin (1), ent-furodysinin (2) and furoircin (3) and ten sterols were characterised in I. mutans, for the first time. Cholesterol (4), cholesta-5, 7-dien-3ß-ol (5) and ergosterol (6) were determined in the sponge from the winter collections, while cholesta-5, 22-dien-3ß-ol (7), 24-methyldesmosterol (8), campesterol (9), stigmasterol (10), γ-ergostenol (11), chondrillasterol (12) and γ-sitosterol (13) were detected in the summer samples. The steroids from the winter collection exhibited cytotoxic activity with IC50 values of 13.0 ± 0.9, 11.1 ± 1.7 and 1.1 ± 0.4 µg/mL, against the mentioned cancer cell lines, respectively, while those from the summer sample, showed greater activity, IC50 = 1.1 ± 0.2 µg/mL against MOLT-4. The purified steroids showed potent MOLT-4 cytotoxic activity, IC50 values = 2.3-7.8 µg/mL. DISCUSSION AND CONCLUSION: The present study suggests that I. mutans is a rich source of cytotoxic steroids, and introduces 3 as new natural product. Considering the high cytotoxic activity of the steroids, these structures could be candidates for anticancer drug development in future research.

Cyanobacteria-From the Oceans to the Potential Biotechnological and Biomedical Applications.

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significant source of novel, bioactive, secondary metabolites, and they are also considered an abundant source of bioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin, cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results in successful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied to medical research have demonstrated an exciting future with great potential to be developed into new medicines. Most of these compounds have exhibited strong pharmacological activities, including neurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so these metabolites could be promising candidates for COVID-19 treatment. Therefore, the effective large-scale production of natural marine products through synthesis is important for resolving the existing issues associated with chemical isolation, including small yields, and may be necessary to better investigate their biological activities. Herein, we highlight the total synthesized and stereochemical determinations of the cyanobacterial bioactive compounds. Furthermore, this review primarily focuses on the biotechnological applications of cyanobacteria, including applications as cosmetics, food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compounds in potential medicinal applications for various human diseases are discussed.

Evaluation of adulteration in distillate samples of Rosa damascena Mill using colorimetric sensor arrays, chemometric tools and dispersive liquid-liquid microextraction-GC-MS.

INTRODUCTION: Rosa damascena Mill distillate and its essential oil are widely used in cosmetics, perfumes and food industries. Therefore, the methods of detection for its authentication is an important issue. OBJECTIVES: We suggest colorimetric sensor array and chemometric methods to discriminate natural Rosa distillate from synthetic adulterates. MATERIAL AND METHODS: The colour responses of 20 indicators spotted on polyvinylidene fluoride (PVDF) substrate were monitored with a flatbed scanner; then their digital representation was analysed with principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and soft independent modelling of class analogy (SIMCA). RESULTS: Accurate discrimination of the diluted- and synthetic-mixture samples from the original ones was achieved by PLS-DA and SIMCA models with error rate of 0.01 and 0, specificity of 0.98 and 1, sensitivity of 1 and 1, and accuracy of 0.98 and 0.96, respectively. Discrimination of the synthetic adulterate from the original samples was achieved with error rate of 0.03 and 0.03, specificity of 0.94 and 0.93, sensitivity of 1 and 1, and accuracy of 0.93 and 0.71 with PLS-DA and SIMCA models, respectively. Moreover, the chemical constituents of the samples were analysed using dispersive liquid-liquid microextraction and gas chromatography-mass spectrometry (GC-MS). The main constituents of the distillate were geraniol, citronellol, and phenylethyl alcohol in different percentages, in both original and synthetic adulterate samples. CONCLUSION: These results point out the successful combination of colorimetric sensor array and PLS-DA and SIMCA as a fast, sensitive and inexpensive screening tool for discrimination of original samples of R. damascena Mill distillate from those prepared from synthetic Rosa essential oils.

Dammarane-type triterpenoid saponins from Salvia russellii Benth.

Three undescribed dammarane-type saponins, russelliinosides A-C, together with a common sterol (ß-sitosterol), an abietane diterpenoid (18-hydroxyferruginol), two oleane triterpenoids (daturaolone and oleanolic acid), an ursane triterpenoid (ursolic acid) as well as three 5-hydroxyflavones (cirsimaritin, eupatorin, and salvigenin) were isolated from a dichloromethane extract of the aerial parts of Salvia russellii Benth. The chemical structures of the aforementioned compounds were characterized, using detailed spectroscopic analyses, including high-resolution mass spectrometry and 1D and 2D NMR (1H-1H COSY, TOCSY, HSQC, HMBC and NOESY) spectroscopy as well as physicochemical properties. Cytotoxic effects of S. russellii extract and the three isolated russelliinosides were tested against MCF-7 human breast and A549 lung cancer, as well as non-cancer NIH/3T3 cells using MTT reduction assay. Russelliinosides A and B exhibited cytotoxic activities with IC50 values of 7.1 and 30.7 µg/ml against MCF-7 and 33.9 and 69.4 µg/ml against A549 cells, respectively, while russelliinoside C did not show cytotoxicity against cancer cells. On the other hand, russelliinoside A showed an IC50 value of 31.5 µg/ml against NIH/3T3 cells, while russelliinosides B and C had no effect on the viability of these non-cancer cells.

Chemometrics-based LC-UV-ESIMS analyses of 50 Salvia species for detecting their antioxidant constituents.

Iran is one of the main hubs for sage's diversity in Asia. Generally, prediction and characterization of the chemical structures of the specialized metabolites that have significant role in the bioactivity of a plant remains a significant challenge. In this study, 50 different accessions of 32 Salvia species in 2015 and 2017 were collected and extracted for their phenolics, using 80 % methanol. LC-PDA-ESIMS analyses was coupled with multivariate analysis to identify the specific metabolites in the plant extracts, responsible for the antioxidant activity. Based on the variable importance in projection (VIP) method on the Genetic algorithm combined with PLS (GA-PLS) models, eighteen peaks were detected as multifunctional compounds. The putative phenolic compounds were attributed to apigenin-O-diglucoside, rutin, cynaroside, luteolin-7-O-glucoronide, apigenin-7-O-glucoside, apigenin-7-O-glucuronide, hispidulin-7-O-glucuronide, hispidulin-7-O-glucoside, rosmarinic acid, salvianolic acid B derivative, cirsimaritin, eupatorin, and carnosol. This investigation showed that the Salvia's extract can facilitate an opportunity for rapid detection, isolation and development of antioxidant agents.

Chemistry, biosynthesis and biological activity of terpenoids and meroterpenoids in bacteria and fungi isolated from different marine habitats.

The marine environment with its vast biological diversity encompasses many organisms that produce bioactive natural products. Marine microorganisms are rich sources of compounds from many structural classes with a multitude of biological activities. The biosynthesis of microbial natural products depends on a variety of biotic and abiotic factors in the marine environment, including temperature, nutrients, salinity and interaction with other microorganisms. Terpenoids, as one of the most important groups of natural products in terrestrial microorganisms are important metabolites for marine microorganisms. Here, we have reviewed the chemistry, biosynthesis and pharmacological activities of terpenoids, extracted from marine microbes, and then survey their potential applications in drug development. We also discussed the different habitats in which marine microorganisms are found including sediments, the flora, such as seaweeds, sea grasses, and mangroves as well as the fauna like sponges and corals. Amongst these habitats, marine sediments are the major source for terpenoids producing microorganisms. The marine bacteria produce mostly meroterpenoids, while the fungi are well known for production of isoprenoids. Interestingly, marine-derived microbial terpenoids have some structural characteristics such as halogenation, which are catalyzed by specific enzymes with distinct substrate specificity. These compounds have anticancer, antibacterial, antifungal, antimalarial and anti-inflammatory properties. The information collected here might provide useful clues for developing new medications.

Antidiabetic and cytotoxic polyhydroxylated oleanane and ursane type triterpenoids from Salvia grossheimii.

Two polyhydroxylated oleanane and seven ursane triterpenoids were isolated from aerial parts of Salvia grossheimii. The chemical structures of the undescribed triterpenoids (1-6) were characterized using 1 and 2 D NMR and ESI-MS spectral data as; 2α, 3ß, 11α -trihydroxy-olean-12- ene (1), 2α, 3ß, 11α-trihydroxy-olean-18-ene (2), 2α- acetoxy-urs-12-ene-3ß, 11α, 20ß-triol (3), 3-keto-urs-12-ene-1ß, 11α, 20ß -triol (4), 2α, 3ß-diacetoxy-urs-12-ene-1ß, 11α, 20ß -triol (5), and 3ß-acetoxy-urs-12-ene-1ß, 11α, 20ß -triol (6). All compounds were evaluated for the in vitro α-glucosidase inhibitory and cytotoxic activities against MCF-7 human cancer cell line. Compounds 1, 2, 4, and 6 showed in vitro α-glucosidase inhibitory activity with IC50 = 43.6-198.4 µM, which were more potent than the antidiabetic medicine, acarbose. The remaining compounds; 3, and 7-9 showed potent cytotoxic activity (IC50 = 6.2-31.9 µM) against the cancerous cell line, while the potent α-glucosidase inhibitors were inactive. Molecular docking analysis and kinetic studies were applied to investigate the structure activity relationships and mechanisms of the human and Saccharomyces cerevisiae α-glucosidase inhibitory of the purified compounds. Comparing the high cytotoxicity and α-glucosidase inhibitory of the oleanane and ursane type triterpenoids suggest them as potential lead compounds for further research in anticancer and antidiabetic research.

Study of the mechanism of action, molecular docking, and dynamics of anticancer terpenoids from Salvia lachnocalyx.

Among specialized metabolites, terpenoids are well-known for their cytotoxic activity. Several of them have been isolated from sage plants and assayed for their potential therapeutic use against cancer. In this study, we report the effects of three potent anticancer terpenoids previously isolated from Salvia lachnocalyx, including geranyl farnesol (1), sahandinone (2), and 4-dehydrosalvilimbinol (3) on cancer cell cycle alterations and reactive oxygen species (ROS) production. Interactions of compounds 1-3 with topoisomerase I were also investigated by using molecular docking and dynamics simulation. Accumulation of cells in sub-G1 phase of the cell cycle indicated that all tested compounds induce apoptosis in MOLT-4 cancer cells. Measurement of ROS production demonstrated that this mechanism is not involved in the induction of apoptosis. We suggest topoisomerase I inhibition as the mechanism of cytotoxic activity of compounds 1-3 based on docking and molecular dynamics (MD) calculations. These natural terpenoids could be considered as good candidates for further development as anticancer agents.

Diterpenoids from Roots of Salvia lachnocalyx; In-silico and In-vitro Toxicity against Human Cancer Cell Lines.

Further investigations on phytochemical constituents of dichloromethane extract from roots of Salvia lachnocalyx (S. lachnocalyx) led to the isolation and identification of eight known diterpenoids from this plant for the first time. The chemical structures of the purified compounds were elucidated using spectroscopic analyses including EI-MS, 1H and 13C NMR and by comparison of the resulting spectra with those reported in the literature. Then, the cytotoxic activity of identified compounds was examined against two human cancer cell lines MCF-7 (human breast adenocarcinoma) and K562 (human chronic myelogenous leukemia). Molecular docking of promising cytotoxic compounds were performed by AutoDock Tools 1.5.4 program in the active site of Topoisomerase I. Eight known diterpenoids; 12-hydroxysapriparaquinone (1), 15-deoxyfuerstione (2), horminon (3), 7α-acetoxyroyleanone (4), 11ß-hydroxymanoyl oxide (5), microstegiol (6), 1-keto-aethiopinone (7) and 14-deoxycoleon U (8) were isolated of dichloromethane extract from roots of salvia lachnocalyx. Compounds 2, 3, 6, and 8 showed cytotoxic activity against MCF-7 (human breast adenocarcinoma) and K562 (human chronic myelogenous leukemia) cell lines with IC50 values in the range of 2.63-11.83 µg/mL. The inhibition of" topoisomerase I" was suggested by molecular docking calculations as the mechanism of cytotoxicity of the tested compounds. According to cytotoxic assay and docking results, it is suggested that compounds 2, 3, 6, and 8 have good potential as anticancer agents.

An "olivomycin A" derivative from a sponge-associated Streptomyces sp. strain SP 85.

We isolated an actinobacterium, Streptomyces sp. strain SP 85 from the marine sponge Dysidea avara. Polyphasic identification of the microorganism showed that the strain SP 85 had high 16S rRNA gene similarity (99%) with Streptomyces olivaceus strain NBRC 12805, while some physiological and biochemical differences were observed. A cytotoxic compound, SP 85 was isolated from the active culture extract of the strain SP 85 by bioassay-guided purification over silica gel column chromatography, preparative TLC, and HPLC. The structure elucidation based on the spectroscopic analysis, including UV, ESI-MS, and 13C NMR data revealed that SP 85 compound is an analog of anti-tumor drug, "olivomycin A". The SP 85 compound showed high cytotoxic activity against three human cancer cell lines, including SW480, HepG2, and MCF7 with IC50 values of 16, 93, and 78 nM, respectively. SP 85 exhibited significantly (2-10 times) higher cytotoxicity against the tumor cell lines in comparison with HUVECs as the normal cell line, which also induced apoptosis in the tested cancerous cell line. This is the first report on the production of an "olivomycin A" derivative by a sponge-associated Streptomyces, showing the great potential of sponge-associated actinobacteria in producing cytotoxic natural products.