Phytochemical and Biological Investigation of an Indigenous Plant of Bangladesh, Gynura procumbens (Lour.) Merr.: Drug Discovery from Nature.

Gynura procumbens (Lour.) Merr. (Family: Asteraceae) is a tropical Asian medicinal plant found in Thailand, China, Malaysia, Indonesia, and Vietnam. It has long been utilized to treat a variety of health concerns in numerous countries around the world, such as renal discomfort, constipation, diabetes mellitus, rheumatism, and hypertension. The chemical investigation resulted in the isolation and characterization of six compounds from the methanol (MeOH) extract of the leaves of Gynura procumbens, which were identified as phytol (1), lupeol (2), stigmasterol (3), friedelanol acetate (4), ß-amyrin (5), and a mixture of stigmasterol and ß-sitosterol (6). In-depth investigations of the high-resolution 1H NMR and 13C NMR spectroscopic data from the isolated compounds, along with comparisons to previously published data, were used to clarify their structures. Among these, the occurrence of Compounds 1 and 4 in this plant are reported for the first time. The crude methanolic extract (CME) and its different partitionates, i.e., petroleum ether (PESF), chloroform (CSF), ethyl acetate (EASF), and aqueous (AQSF) soluble fractions, were subjected to antioxidant, cytotoxic, thrombolytic, and anti-diabetic activities. In a DPPH free radical scavenging assay, EASF showed the maximum activity, with an IC50 value of 10.78 µg/mL. On the other hand, CSF displayed the highest cytotoxic effect with an LC50 value of 1.94 µg/mL compared to 0.464 µg/mL for vincristine sulphate. In a thrombolytic assay, the crude methanolic extract exhibited the highest activity (63.77%) compared to standard streptokinase (70.78%). During the assay for anti-diabetic activity, the PESF showed 70.37% of glucose-lowering activity, where standard glibenclamide showed 63.24% of glucose-reducing activity.

Isolation and In Silico Prediction of Potential Drug-like Compounds with a New Dimeric Prenylated Quinolone Alkaloid from Zanthoxylum rhetsa (Roxb.) Root Extracts Targeted against SARS-CoV-2 (Mpro).

A new dimeric prenylated quinolone alkaloid, named 2,11-didemethoxy-vepridimerine A, was isolated from the root bark of Zanthoxylum rhetsa, together with twelve known compounds. The structure of the new compound was elucidated on the basis of spectroscopic investigations (NMR and Mass). The interaction of the isolated compounds with the main protease of SARS-CoV-2 (Mpro) was evaluated using molecular docking followed by MD simulations. The result suggests that 2,11-didemethoxy-vepridimerine A, the new compound, has the highest negative binding affinity against the Mpro with a free energy of binding of -8.5 Kcal/mol, indicating interaction with the Mpro. This interaction was further validated by 100 ns MD simulation. This implies that the isolated new compound, which can be employed as a lead compound for an Mpro-targeting drug discovery program, may be able to block the action of Mpro.

One-year outcomes of patients undergoing complex percutaneous coronary intervention with three contemporary drug-eluting stents.

OBJECTIVES: We aimed to evaluate the 1-year outcomes of three everolimus-eluting stents (EES) for complex percutaneous coronary intervention (PCI). BACKGROUND: It is controversial whether contemporary bioresorbable-polymer drug-eluting stents (BP-DES) are associated with better outcomes compared with durable-polymer DES (DP-DES). METHODS: Patients undergoing PCI with cobalt-chromium (CoCr)-DP-EES (Xience), platinum-chromium (PtCr)-DP-EES (Promus), or PtCr-BP-EES (Synergy) at one high-volume institution between 2015 and 2017 were included. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of death, myocardial infarction, and target-vessel revascularization. Associations were also examined in patients undergoing complex PCI. Multivariable analysis was conducted to adjust for baseline differences across groups. RESULTS: We included n = 5,446 patients (CoCr-DP-EES, n = 3,177; PtCr-DP-EES, n = 1,555; PtCr-BP-EES, n = 714). Patients treated with PtCr-BP-EES had higher comorbidity burden and procedural complexity. At 1 year, MACE rates were 8.9% for CoCr-DP-EES versus 8.9% for PtCr-DP-EES versus 8.6% for PtCr-BP-EES (p = .97). The incidence of definite/probable stent thrombosis (ST) was also similar (0.6 vs. 0.4 vs. 0.3%, p = .69). Complex PCI was performed in n = 2,894/5,446 (53.1%). At 1 year, MACE rates were 11.5 versus 10.7 versus 10.3%, respectively (p = .83). The incidence of definite/probable ST was also similar (0.9 vs. 0.3 vs. 0.3%, p = .22). On multivariable analysis, stent type was not an independent predictor of MACE either in the overall or in the complex PCI population. CONCLUSIONS: We observed comparable 1-year rates of MACE and definite/probable ST in patients undergoing PCI with CoCr-DP-EES, PtCr-DP-EES, and PtCr-BP-EES. Results were unchanged among patients undergoing complex PCI. Future multicenter randomized studies should confirm and extend our findings.

Side branch fractional flow reserve after provisional stenting of calcified bifurcation lesions: The ORBID-FFR study.

OBJECTIVES: We examined the incidence of side branch (SB) compromise after provisional stenting of calcified bifurcation lesions treated with rotational atherectomy (RA) or cutting balloon angioplasty (CBA) and the utility of optical coherence tomography (OCT) to detect functionally significant SB stenoses. BACKGROUND: The comparative impact of RA versus CBA on SB compromise and functional significance remains poorly characterized. METHODS: Seventy-one consecutive patients with 71 calcified bifurcation lesions with angiographically intermediate SB stenoses were randomized to RA (n = 35) or CBA (n = 36). The primary endpoint was SB compromise defined as SB diameter stenosis ≥70%, SB dissection or thrombolysis in myocardial infarction flow grade < 3 after provisional stenting. Secondary endpoints included SB FFR in noncompromised SBs and its correlation with SB ostium area (SBOA) assessed by three-dimensional OCT. RESULTS: SB compromise after provisional stenting was observed in 7 (20.0%) lesions that underwent RA and in 9 (25.0%) lesions treated with CBA (p = .62). Mean SB FFR was 0.83 ± 0.08 and was similar between the study arms. Functionally significant SB stenosis (FFR ≤ 0.80) was detected in 17(30.9%) angiographically noncompromised SBs. SBOA after stenting was an independent predictor of FFR ≤ 0.80 (OR 0.002, 95% CI: 0.00-0.15, p = .002). The optimal cutoff value for SBOA to predict functionally significant SB stenosis was 0.76 mm2 (sensitivity 82%, specificity 89% and area under the curve 0.92, 95% CI: 0.84-0.99). CONCLUSIONS: The rates of SB compromise and functionally significant stenosis after provisional stenting of calcified bifurcation lesions were similar between two lesion preparation strategies. OCT SBOA can detect SB branches with FFR ≤ 0.80 with high sensitivity and specificity.

Cardiovascular outcomes after percutaneous coronary intervention on bifurcation lesions with moderate to severe coronary calcium: A single-center registry study.

BACKGROUND: Both target vessel calcification and target vessel bifurcation are associated with worse outcomes following percutaneous coronary intervention (PCI). Whether these entities in combination interact to influence outcomes after PCI of complex coronary disease is not known. OBJECTIVES: This study evaluated the association of target vessel bifurcation and target vessel calcification, alone and in combination, with adverse events following PCI. METHODS: Registry data from 21,165 patients who underwent PCI with drug-eluting stents (DES) between January 2009 and December 2017 were analyzed. Patients were divided into four groups according to the presence or absence of target vessel bifurcation and presence of none/mild or moderate/severe target vessel calcification on angiography. Associations between lesion groups and 1 year major adverse cardiac events (MACE) were examined using Cox regression analysis. RESULTS: At 1 year, unadjusted rates of MACE, death, myocardial infarction (MI), as well as stent thrombosis were highest in the group with both bifurcation lesion and moderate/severe calcification. After adjusting for confounders such as age, renal disease, and smoking, hazard ratios for MACE were 1.14 (95%CI 0.99-1.33) for bifurcation with none/mild calcification, 1.21 (95%CI 1.06-1.38) for no bifurcation and moderate/severe calcification, and 1.37 (95%CI 1.14-1.64) for bifurcation and moderate severe calcification, compared to patients with no bifurcation and none/mild calcification. CONCLUSIONS: The presence of a bifurcating target vessel with moderate/severe calcification is associated with a higher risk of adverse outcomes than either attribute alone. New approaches are needed to improve outcomes in this subset of patients with complex coronary artery disease.

Predictors of side branch compromise in calcified bifurcation lesions treated with orbital atherectomy.

OBJECTIVES: The aim of the study was to identify the predictors of side branch (SB) compromise in severely calcified bifurcation lesions treated with orbital atherectomy (OA). BACKGROUND: SB compromise remains a major complication of bifurcation lesion percutaneous coronary intervention (PCI). Higher prevalence of lipid-rich plaques and spotty calcification by optical coherence tomography (OCT) and SB ostial stenosis by angiography have been previously suggested as predictors of SB occlusion after main vessel (MV) stenting. METHODS: Patients with chronic stable angina and severely calcified bifurcation lesions, in whom provisional stenting strategy was planned, were enrolled in the study. OA was used for lesion preparation in all cases. OCT imaging of the MV was performed before and after stenting. SB compromise was defined as a composite of SB occlusion (TIMI flow grade ≤ 2) and SB intervention after MV stenting. RESULTS: Thirty stable CAD patients with 30 severely calcified bifurcation lesions were included in the study. Twelve patients (40%) had a compromised SB after MV stenting. Compromised SB was characterized by a greater angiographic diameter stenosis (55.4 ± 8.1% vs. 35.0 ± 14.4%, P < 0.01) and a smaller minimal lumen diameters (0.79 ± 0.17 vs. 1.12 ± 0.30 mm, P = 0.002) before PCI compared to noncompromised SB. The prevalence of OCT lipid-rich plaques was low and did not differ between the groups (18 vs. 19%, P = 0.68). There was no difference in other OCT plaque characteristics including the presence of spotty calcification. CONCLUSION: The severity of SB ostial disease and not MV plaque morphology contributed to SB compromise in severely calcified bifurcation lesions.

Prevalence, correlates, and impact of coronary calcification on adverse events following PCI with newer-generation DES: Findings from a large multiethnic registry.

OBJECTIVES: We sought to determine the prevalence, predictors, and clinical impact of target lesion calcification in patients undergoing percutaneous coronary intervention (PCI) with newer generation drug-eluting stents (DES) and devices. BACKGROUND: Coronary calcification is independently associated with adverse outcomes following PCI. While newer DES and contemporary devices are considered safer and more efficacious, their influence on outcomes following PCI of heavily calcified lesions is unknown. METHODS: We performed a retrospective analysis of a large, multiethnic cohort of patients undergoing PCI with new generation DES at an academic center between 2009 and 2013. Coronary calcification was qualitatively assessed as none/mild, moderate, or severe. Independent demographic, clinical, and anatomic predictors of moderate/severe calcification were identified using logistic regression. Associations between coronary calcification and 1-year MACE (death, myocardial infarction, or target vessel revascularization) were examined using Cox modeling. RESULTS: Compared to patients with none/mild (n = 10,180; 82.0%), those with moderate (n = 1,271; 10.0%) or severe (n = 994; 8.0%) calcification were older, more often Caucasian, had more complex target lesions, and worse renal function. The strongest demographic, clinical, and anatomic correlates of moderate/severe calcification were age, Caucasian race, renal dysfunction, lesion length, and left main location. Unadjusted MACE rates among those with none/mild, moderate, and severe calcification were 8.3, 14.6, and 17.8%, respectively (P < 0.001). After multivariable adjustment, the hazard ratio (95% CI) for MACE associated with moderate or severe coronary calcification was 1.63. CONCLUSIONS: Target lesion calcification remains independently associated with adverse outcomes in patients treated with newer generation DES and modern devices.

Crispenes F and G, cis-Clerodane Furanoditerpenoids from Tinospora crispa, Inhibit STAT3 Dimerization.

Two new cis-clerodane-type furanoditerpenes, crispenes F and G (1 and 2), together with seven known compounds, were isolated from the stems of Tinospora crispa. Crispenes F and G (1 and 2) inhibited STAT3 dimerization in a cell-free fluorescent polarization assay and were found to have significant cytotoxicity against a STAT3-dependent MDA-MB 231 breast cancer cell line, while being inactive in a STAT3-null A4 cell line. These two compounds share structural similarities with a previously reported STAT3 inhibitor, crispene E, isolated from the same plant. Molecular docking studies suggested that the molecules inhibit STAT3 by interacting with its SH2 domain.

Anti-Staphylococcal Calopins from Fruiting Bodies of Caloboletus radicans.

Three new and seven known calopins were isolated from Caloboletus radicans. The structures of the new cyclocalopins, 8-deacetylcyclocalopin B (1), cyclocalopin A-15-ol (2), and 12,15-dimethoxycyclocalopin A (3), were mainly elucidated by NMR and MS data analysis. The stereochemistry of 1-3 was assigned based on NOE correlations and coupling constants and by comparison of their CD spectra with those of similar known calopins. While 1-10 were inactive against two cancer cell lines, they displayed anti-staphylococcal activity against methicillin-resistant Staphylococcus aureus strains (MRSA) with MIC values of 16-256 µg/mL. Moreover, some calopins were active against the fish pathogen Enterococcus faecalis F1B1.

Fusaproliferin, a Fungal Mycotoxin, Shows Cytotoxicity against Pancreatic Cancer Cell Lines.

As a part of our ongoing research on endophytic fungi, we have isolated a sesterterpene mycotoxin, fusaproliferin (FUS), from a Fusarium solani strain, which is associated with the plant Aglaonema hookerianum Schott. FUS showed rapid and sub-micromolar IC50 against pancreatic cancer cell lines. Time-dependent survival analysis and microscopy imaging showed rapid morphological changes in cancer cell lines 4 h after incubation with FUS. This provides a new chemical scaffold that can be further developed to obtain more potent synthetic agents against pancreatic cancer.

Plaque morphology predictors of side branch occlusion after provisional stenting in coronary bifurcation lesion: Results of optical coherence tomography bifurcation study (ORBID).

OBJECTIVES: The aim of this study was to identify the predictors of side branch (SB) ostial stenosis developed after provisional stenting of the main vessel (MV) using optical coherence tomography (OCT). BACKGROUND: Provisional stenting remains the main approach to treatment of bifurcation lesions; however, it may result in the narrowing of SB ostium. There is little information about underlying plaque morphology of the MV lesion and its potential impact on the SB after provisional stenting. METHODS: Patients with stable coronary disease with angiographic MV lesion not involving SB were included in a prospective single center study. The primary outcome was significant SB ostium stenosis (SBOS), defined as residual stenosis of >50% after MV stenting. RESULTS: Thirty bifurcation lesions in 30 patients were analyzed in the study. Poststenting significant SBOS was observed in 30% of patients. The MV lesions with SBOS > 50% were characterized by a higher prevalence of lipid rich plaques (100 vs. 64%, p = 0.040) and spotty calcifications (60 vs. 0%, p = 0.005). Maximal lipid arcs were greater (257° vs. 132°, p = 0.001) and lipid volume index was higher (1380 vs. 574, p = 0.012) in the SBOS >50% group. Multivariate logistic regression analysis identified maximal lipid arc (odds ratio (OR): 1.014, p = 0.038) and the presence of lipid plaque contralateral to SB ostium (OR: 8.14, p = 0.046) before stenting as independent predictors of significant SBOS after PCI. CONCLUSIONS: High lipid content of the MV lesion and a contralateral location of lipid in the bifurcation area may contribute to SBOS after provisional stenting. © 2016 Wiley Periodicals, Inc.

Cytotoxic Naphthoquinone and Azaanthraquinone Derivatives from an Endophytic Fusarium solani.

Bioactivity-guided fractionation of the ethyl acetate extract obtained from the culture of the endophytic fungus Fusarium solani resulted in the isolation of one new naphthoquinone, 9-desmethylherbarine (1), and two azaanthraquinone derivatives, 7-desmethylscorpinone (2) and 7-desmethyl-6-methylbostrycoidin (3), along with four known compounds. Their structures were elucidated by spectral analysis, as well as a direct comparison of spectral data with those of known compounds. Azaanthraquinones 2 and 3 showed cytotoxic activity against four human tumor cell lines, MDA MB 231, MIA PaCa2, HeLa, and NCI H1975. A molecular docking study suggested DNA interactions as the mode of action of these naphthoquinones and azaanthraquinones.

Gageopeptins A and B, new inhibitors of zoospore motility of the phytopathogen Phytophthora capsici from a marine-derived bacterium Bacillus sp. 109GGC020.

The motility of zoospores is critical in the disease cycles of the peronosporomycetes that cause devastating diseases in plants, fishes, vertebrates, and microbes. In the course of screening for secondary metabolites regulating the motility of zoospores of Phytophthora capsici, we discovered two new inhibitors from the ethyl acetate extract of the fermentation broth of a marine-derived strain Bacillus sp. 109GGC020. The structures of these novel metabolites were elucidated as new cyclic lipopeptides and named gageopeptins A (1) and B (2) by spectroscopic analyses including high resolution MS and extensive 1D and 2D NMR. The stereoconfigurations of 1 and 2 were assigned based on the chemical derivatization studies and reviews of the literature data. Although compounds 1 and 2 impaired the motility of zoospores of P. capsici in dose- and time-dependent manners, compound 1 (IC50 = 1 µg/ml) was an approximately 400-fold stronger motility inhibitor than 2 (IC50 = 400 µg/ml). Interestingly, the zoospores halted by compound 1 were subsequently lysed at higher concentrations (IC50 = 50 µg/ml). Compounds 1 and 2 were also tested against some bacteria and fungi by broth dilution assay, and exhibited moderate antibacterial and good antifungal activities.

Crispene E, a cis-clerodane diterpene inhibits STAT3 dimerization in breast cancer cells.

Crispene E, a new clerodane-type diterpene, inhibited STAT3 dimerization in a cell-free fluorescent polarisation assay and was found to have significant toxicity against STAT3-dependent MDA-MB 231 breast cancer cell line and selectively inhibited the expression of STAT3 and STAT3 target genes cyclin D1, Fascin and bcl-2. Molecular docking studies suggest the molecule inhibits STAT3 by interacting with its SH2 domain. The compound has been isolated from Tinospora crispa and characterized using standard spectroscopic techniques.

Exploration and evaluation of antioxidant activity in isolated phenolics from Jasminum scandens (retz) vahl.

Given the widespread and established use of Jasminum scandens (Retz) Vahl, a member of the Oleacea family, this study aimed to identify and characterise secondary metabolites derived from the plant, with the objective of evaluating their potential biological activities. Using chromatographic separations techniques based on molecular weight and polarity, various VLC fractions of the plant were purified. These fractions yielded seven compounds- 2-(4-hydroxyphenyl)-ethanol (1), 2-(4-hydroxy-3-methoxy-phenyl)-ethanol (2), 1-(4-hydroxy-3-methoxy-phenyl)-1,2,3-propanetriol (3), 1-(4-hydroxy-3,5-dimethoxy-phenyl)-1,2,3-propanetriol (4), lupeol (5), ß-sitosterol (6), and methyl linoleate (7), which have never been previously reported in this plant. Out of the seven identified compounds, compounds 3 and 4 had the greatest capacity to scavenge free radicals with IC50 values of 3.81 µg/ml and 4.08 µg/ml, respectively when compared to the standard Butylated Hydroxy Toluene (BHT) with IC50 value of 6.54 µg/ml.

Two rare flavonoid glycosides from Litsea glutinosa (Lour.) C. B. Rob.: experimental and computational approaches endorse antidiabetic potentiality.

BACKGROUND: Litsea glutinosa (Lour.) C. B. Rob. belongs to the Litsea genus and is categorized under the family of Lauraceae. The study aimed to investigate the phytoconstituents and pharmacological properties of methanol extract of leaves of Litsea glutinosa, focusing on antidiabetic activity via in vivo and in silico techniques. METHODS: Extensive chromatographic and spectroscopic techniques were applied to isolate and characterize the constituents from the L. glutinosa plant species. The antidiabetic activity was studied in streptozotocin-induced diabetes mice, and the computational study of the isolated compounds was carried out by utilizing AutoDock Vina programs. In addition, the pharmacokinetic properties in terms of absorption, distribution, metabolism and excretion (ADME) and toxicological profiles of the isolated compounds were examined via in silico techniques. RESULTS: In the present study, two flavonoid glycosides 4΄-O-methyl (2 ̋,4 ̋-di-E-p-coumaroyl) afzelin (1) and quercetin 3-O-(2 ̋,4 ̋-di-E-p-coumaroyl)-α-L-rhamnopyranoside (2) were isolated from the leaves of L. glutinosa and characterized by 1H and 13C NMR, COSY, HSQC, HMBC, and mass spectral data. Although compounds 1 and 2 have been reported twice from Machilis litseifolia and Lindera akoensis, and Machilis litseifolia and Mammea longifolia, respectively, this is the first report of this isolation from a Litsea species. Administering the methanolic extract of L. glutinosa at doses of 300 and 500 mg/kg/day to mice with diabetes induced by streptozotocin led to a significant decrease in fasting blood glucose levels (p < 0.05) starting from the 7th day of treatment. Besides, the computational study and PASS analysis endorsed the current in vivo findings that the both isolated compounds exerted higher binding affinities to human pancreatic α-amylase and aldose reductase than the conventional drugs. The in silico ADMET analysis revealed that the both isolated compounds have a favorable pharmacokinetic and safety profile suitable for human consumption. CONCLUSION: According to the current outcomes obtained from in vivo and in silico techniques, the leaf extract of L. glutinosa could be a natural remedy for treating diabetes, and the isolated phytoconstituents could be applied against various illnesses, mainly hyperglycemia. However, more investigations are required for extensive phytochemical isolation and pharmacological activities of these phytoconstituents against broader targets with exact mechanisms of action.

Chemico-pharmacological and computational studies of Ophiorrhiza fasciculata D. Don and Psychotria silhetensis Hook. f. focusing cytotoxic, thrombolytic, anti-inflammatory, antioxidant, and antibacterial properties.

The current study sought to examine the pharmacological potentials of crude methanolic extracts of Ophiorrhiza fasciculata and Psychotria silhetensis, as well as their various solvent fractionates, with a focus on cytotoxic, thrombolytic, membrane stabilizing, antioxidant, and antibacterial activities via in vitro and in silico approaches. The extensive chromatographic and spectroscopic analyses confirmed and characterized two compounds as (±)-licarin B (1) and stigmasterol (2) from O. fasciculata and P. silhetensis, respectively. Petroleum ether soluble fraction of O. fasciculata and the aqueous soluble fraction of P. silhetensis showed the lowest 50% lethal concentrations (1.41 and 1.94 µg/mL, respectively) in brine shrimp bioassay. Likewise, petroleum ether soluble fraction of O. fasciculata and aqueous soluble fraction of P. silhetensis showed the highest thrombolytic activity with 46.66% and 50.10% lyses of the clot, respectively. The methanol and dichloromethane soluble fractions of O. fasciculata reduced erythrocyte hemolysis by 64.03% and 37.08%, respectively, under hypotonic and heat-induced conditions, compared to 81.97% and 42.12% for standard acetylsalicylic acid. In antioxidant activity test, aqueous soluble fraction O. fasciculata (IC50 = 7.22 µg/mL) revealed promising antioxidant potentialities in comparison to standard butylated hydroxytoluene (IC50 = 21.20 µg/mL). In antibacterial screening, chloroform, and dichloromethane soluble fractions of P. silhetensis showed a mild antibacterial activity compared with the standard drug ciprofloxacin. Additionally, the molecular docking study corroborated the current in vitro findings, and the isolated two constituents had higher binding affinities toward epidermal growth factor receptor, tissue plasminogen activator, vFLIP-IKK gamma stapled peptide dimer, glutathione reductase, and dihydrofolate reductase enzyme than their corresponding standard drugs. In addition, the both isolated compounds exerted favorable pharmacokinetics (absorption, distribution, metabolism, excretion) and toxicological profiles with drug-like qualities in computational-based ADMET and drug likeliness analyses. The current research suggests that both plants have potential as a natural treatment for treating thrombosis, inflammation, and oxidative stress. However, more thorough research is required to thoroughly screen for phytochemicals and pinpoint the precise mechanisms of action of the bioactive metabolites derived from these plants against a broad range of molecular targets.

Four new isoflavones from Derris scandens and their in vitro antiproliferative effects.

Four new compounds (derriscandenon D (1), E (2), F (3), G (4)) and six known isoflavones (warangalone (5), millewanin E (6), rhynedlin A (7), 6,8-diprenylgenistein (8), isolupalbigenin (9), isoscandinone (10)) were isolated from the acetone extract of the branches of Derris scandens. These compounds were assayed for cell viability using the human lung carcinoma cell line A549, colorectal carcinoma cell line Colo205, epidermoid carcinoma cell line KB, the human acute lymphoblastic leukaemia cell line NALM-6, and human dermal fibroblasts. Compounds 2 and 3 significantly decreased the viability of KB cells, with IC50 values of 2.7 and 12.9 µM, respectively. In addition, compounds 2 and 3 reduced the mitochondrial membrane potential in KB cells. Compounds 2 and 3 strongly down-regulated the cell viability of cell lines KB and NALM-6, achieving IC50 values of 2.7 and 0.9 µM, respectively, compared with the positive control staurosporine at 1.25 and 0.01 µM, respectively.

Physicochemical, Pharmacokinetic and Cytotoxicity of the Compounds Isolated from an Endophyte Fusarium oxysporum: In Vitro and In Silico Approaches.

The present study was intended to characterize the secondary metabolites of the endophyte Fusarium oxysporum isolated from the plant Aglaonema hookerianum Schott. And to investigate the cytotoxic and other pharmacological properties of the isolated compounds as part of the drug discovery and development process. Different chromatographic techniques were adopted to isolate the bioactive compounds that were identified by spectroscopic techniques. The cytotoxic properties of the compounds were assessed in the Vero cell line via the trypan blue method. Moreover, physicochemical, pharmacokinetic, bioactivity and toxicity profiles of the compounds were also investigated through in silico approaches. After careful spectral analysis, the isolated compounds were identified as 3ß,5α-dihydroxy-ergosta-7,22-dien-6-one (1), 3ß,5α,9α-trihydroxy-ergosta-7,22-dien-6-one (2), p-hydroxybenzaldehyde (3), 3-(R)-7-butyl-6,8-dihydroxy-3-pent-11-enylisochroman-1-one (4) and beauvericin (5). An in vitro study in the Vero cell line revealed that the presence of the compounds reduced the number of cells, as well as the percentage of viable cells, in most cases. An in silico cytotoxic analysis revealed that compounds 1, 2 and 5 might be explored as cytotoxic agents. Moreover, compounds 3 and 4 were found to be highly mutagenic. The present study suggested that further thorough investigations are necessary to use these molecules as leads for the cytotoxic drug development process.

Relationship between hemoglobin A1C and characteristics of plaque vulnerability in stable coronary disease: an optical coherence tomography study.

Patients with diabetes mellitus are at increased risk of cardiovascular events. We aimed to analyze the impact of serum HbA1c levels on coronary plaque characteristics in stable coronary disease. Two hundred sixty-one patients who underwent optical coherence tomography (OCT) examination before elective percutaneous coronary intervention for a de novo obstructive lesions were included in this single-center retrospective analysis. Patients were divided into tertiles according to HbA1c level (tertile 1: HbA1c < 6.3%, tertile 2: 6.3 ≤ HbA1c < 7.8%, tertile 3: HbA1c ≥ 7.8%) and OCT findings were compared. Fibrous cap thickness (FCT) was significantly thinner in tertile 3 compared to tertile 1 and tertile 2 (103.9 ± 48.2 µm [tertile 1] vs. 107.5 ± 60.6 µm [tertile 2] vs. 86.2 ± 35.8 µm [tertile 3], p = 0.03). Higher prevalence of thin-cap fibroatheroma (TCFA) was observed in tertile 3 vs tertile 1 and tertile 2 (19.5% [tertile 1] vs. 19.5% [tertile 2] vs. 33.3% [tertile 3], p = 0.04). HbA1c inversely correlated with FCT (beta coefficient - 4.89, 95% confidence interval - 8.40 to - 1.39, p < 0.01). The logistic regression model revealed that the probability of having TCFA was positively associated with HbA1c with a small change in the range of low and medium HbA1c and a big change in the range of high HbA1c. Furthermore, minimal lumen area and reference lumen area were smaller in tertile 3. In patients with stable coronary disease, high serum HbA1c levels are associated with higher plaque burden and thinner FCT on OCT, while low and medium HbA1c levels result in similar plaque vulnerability.