Weak Activity Research Articles

Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV).

The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity invitro, and observational and clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended in therapeutic guidelines and their antiviral activity invivo has not been characterised. PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos. We recruited low-risk adult outpatients aged 18-50 with early symptomatic COVID-19 (symptoms <4 days) between 5 April 2022 and 8 May 2023. Patients were assigned using block randomisation to one of eleven treatment arms including oral fluoxetine (40mg/day for 7 days), or no study drug. Uniform randomisation ratios were applied across the active treatment groups while the no study drug group comprised ≥20% of patients at all times. The primary endpoint was the rate of oropharyngeal viral clearance assessed until day 7. Measurements were taken daily between days 0 and 7 and analysed in a modified intention-to-treat population (>2 days follow-up).The viral clearance rate was estimated under a Bayesian hierarchical linear model fitted to the log10 viral densities measured in standardised duplicate oropharyngeal swab eluates taken daily over one week (18 measurements per patient). Secondary endpoints were all-cause hospital admission at 28 days, and time to resolution of fever and symptoms. This ongoing trial is registered at ClinicalTrials.gov (NCT05041907). 271 patients were concurrently randomised to either fluoxetine (n=120) or no study drug (n=151). All patients had received at least one COVID-19 vaccine dose and 67% were female (182/271). In the primary analysis, viral clearance rates following fluoxetine were compatible with a small or no increase relative to the no study drug arm (15% increase; 95% credible interval (CrI):-2 to 34%). There were no deaths or hospitalisations in either arm. There were no significant differences in times to symptom resolution or fever clearance between the fluoxetine and the no study drug arms (although only a quarter of patients were febrile at baseline). Fluoxetine was well tolerated, there were no serious adverse events and only one grade 3 adverse event in the intervention arm. Overall, the evidence from this study is compatible with fluoxetine having a weak invivo antiviral activity against SARS-CoV-2, although the primary endpoint is also compatible with no effect. This level of antiviral efficacy is substantially less than with other currently available antiviral drugs. Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator.

АНТИБИОТИЧЕСКАЯ АКТИВНОСТЬ ПРЕДСТАВИТЕЛЕЙ СЕМ. BACILLACEAE В ОТНОШЕНИИ RHIZOPUS STOLONIFER

The aim of the study is to test the antibiotic activity of representatives of the Bacillaceae family against the mycelial fungus Rhizopus stolonifer Vuillemin (1902). The strains of Bacillus altitudinis, Bacillus atrophaeus, Bacillus cereus, Bacillus megaterium, Bacillus simplex, Bacillus subtilis, Peribacillus simplex and Bacillus sp. were used, isolated by the authors from agricultural soils of the Krasnoyarsk Region and in previous studies showing antagonism against phytopathogenic fungi Fusarium spp., Alternaria spp., Sclerotinia sclerotiorum, Geotrichum candidum, as well as against seed mold pathogens of the genus Aspergillus, Penicillium and Mucor. The antibiotic activity of the studied strains against R. stolonifer was assessed in Petri dishes using the counter culture method. The area of the R. stolonifer colony in the presence of the antagonist strain as a percentage of the control variant (without the antagonist) after 10 days of incubation at a temperature of (25 ± 1) °C was used as an indicator of antibiotic activity. Of the 21 tested strains, 4 did not exhibit antagonism towards R. stolonifer; 16 strains showed weak or moderate antibiotic activity (reduction in the area of fungal colonies by 29.1–79.1 % relative to the control); 1 strain showed high antibiotic activity (reduction in the area of R. stolonifer colonies by 92 % relative to the control). No relationship was found between the antibiotic activity of the studied strains towards R. stolonifer and the taxonomically close zygomycete Mucor sp. (Spearman's rank correlation coefficient Rs = 0.272, statistically insignificant). Based on the results of the studies, the B. atrophaeus RSA9 strain can be proposed as an agent for the biological method of controlling R. stolonifer.

Stereoselective Synthesis and Antimicrobial Studies of Allo-Gibberic Acid-Based 2,4-Diaminopyrimidine Chimeras

Background: Gibberellins (GAs) are a family of tetracyclic ent-kaurenoid diterpenes found widely in several commonly used plants. Besides agricultural applications, gibberellins play an important role in the synthesis of bioactive compounds, especially those with antiproliferative and antibacterial activity. Methods: A series of gibberellic acid-based 2,4-diaminopyrimidines was designed and synthesized from commercially available gibberellic acid. The antimicrobial activity of the prepared compounds was also explored in B. subtilis, S. aureus, E. coli, and P. aeruginosa bacteria, as well as in C. krusei and C. albicans fungi. Results: The treatment of gibberellic acid with hydrochloric acid under reflux conditions resulted in aromatization followed by rearrangement to form allo-gibberic acid. The key intermediate azido alcohol was prepared according to the literature methods. The second key intermediate azidotriol was synthesized by the stereoselective dihydroxylation of the allylic function by the osmium (VIII)-tetroxide/NMO system. Starting from azide intermediates, click reactions were also carried out with 4-monoamino- and 2,4-diaminopyrimidines functionalized with the N-propargyl group. The new chimeric compounds, coupled with gibberellins thus obtained, were characterized by 1D- and 2D-NMR techniques and HRMS measurements. While the 4-monoamino-substituted derivatives exhibited only weak antibacterial activity, they demonstrated significant antifungal effectiveness against C. krusei. In general, 5-chloro-substituted pyrimidine derivatives displayed more consistent biological activities compared to their 5-fluoro counterparts, with the exception of one derivative, which showed acceptable activity against both C. krusei and C. albicans. The two derivatives featuring 5-chloro and 2-((4-(trifluoromethyl)phenyl)amino substituents proved to be highly effective against P. aeruginosa, making them promising candidates for further research. Aiming to elucidate the molecular interactions between the active compounds and their potential targets, molecular docking studies were conducted using AutoDock Vina 1.1.2. involving the most active compounds against P. aeruginosa. Conclusions: The biological effects of 2-monoamino or 2,4-diamino substitution as well as the effect of chloro or fluoro substitution at position 5 of the pyrimidine ring combined with the allo-gibberic acid moiety were determined. Compounds with selective antibacterial activity against P. aeruginosa as well as selective antifungal activity against C. krusei and C. albicans fungi were identified.

Sesquiterpenoids from &lt;i&gt;Dysoxylum amooroides&lt;/i&gt; Stem Bark: Isolation, Structure Determination, and Cytotoxicity Against MCF-7 Breast Cancer Cells

Three sesquiterpenoids, guaianediol (1), alismol (2), and spathulenol (3), were isolated from the n-hexane and ethyl acetate extracts of the stem bark of Dysoxylum amooroides. The three compounds were found in D. amooroides species for the first time. The structures of the isolated compounds were identified and established based on an extensive spectroscopic analysis involving HR-TOF-ESI-MS, IR, and NMR data, as well as a comparison with the previously reported works of literature. Compounds 1-3 were further assessed for cytotoxic effects against MCF-7 breast cancer cells. Guaianediol (1) showed inactive activity with IC50 &gt; 100 µM, alismol (2) showed weak activity with IC50 value of 82.1 µM and spathulenol (3) showed considerable activity with an IC50 value of 15.2 µM. A brief structure-activity relationship and comparison with the previous works were also discussed to understand better the role of guaiane- and aromadendrane-type sesquiterpenoids in the biological activity perspective.

Dose-dependent enhancement of in vitro osteogenic activity on strontium-decorated polyetheretherketone

Polyetheretherketone (PEEK) is widely used in orthopedic and dental implants due to its excellent mechanical properties, chemical stability, and biocompatibility. However, its inherently bioinert nature makes it present weak osteogenic activity, which greatly restricts its clinical adoption. Herein, strontium (Sr) is incorporated onto the surface of PEEK using mussel-inspired polydopamine coating to improve its osteogenic activity. X-ray photoelectron spectroscopy and ion release assay results confirm that different concentrations of Sr are incorporated onto the PEEK substrate surfaces. The strontium-modified PEEK samples show a stable Sr ion release in 35 days of detection. Better results of MC3T3-E1 pre-osteoblasts adhesion, spreading, and proliferation can be observed in strontium-modified PEEK groups, which demonstrates strontium-modified PEEK samples with the improved MC3T3-E1 pre-osteoblasts compatibility. The boosted osteogenic activity of strontium-modified PEEK samples has been demonstrated by the better performed of ALP activity, extracellular matrix mineralization, collagen secretion, and the remarkable up-regulation of ALP, OCN, OPN, Runx2, Col-I, BSP, and OSX of the MC3T3-E1 pre-osteoblasts. Additionally, the strontium-modified PEEK samples exhibit a dose-dependent enhancement of osteoblasts compatibility and osteogenic activity, and the PEEK-Sr10 group shows the best. These findings indicate that strontium-decorated PEEK implants show promising application in orthopedic and dental implants.

Metabolic Blockade-Based Genome Mining of Malbranchea circinata SDU050: Discovery of Diverse Secondary Metabolites.

Malbranchea circinata SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation and identification of four classes of secondary metabolites from wild-type M. circinata SDU050, alongside five additional metabolite classes, including three novel cytochalasins (7-9), obtained from a mutant strain through the metabolic blockade strategy. Furthermore, bioinformatic analysis of the BGC associated with the isocoumarin sclerin (1) enabled the deduction of its biosynthetic pathway based on gene function predictions. Bioactivity assays demonstrated that sclerin (1) and (-)-mycousnine (10) exhibited weak antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Bacillus subtilis. These findings underscore the chemical diversity and biosynthetic potential of M. circinata SDU050 and highlight an effective strategy for exploring marine fungal metabolites.

Phytochemical Test and Antioxidant Activity Of Various Organs Of The Golden Banana (Musa acuminata Colla)

The golden banana (Musa acuminata Colla) is a typical banana plant in Rokan Hilir. Some parts of the golden banana plant are generally used, however, various other banana organs such as fruit skin, stem midrib, bractea, and golden banana flowers in Rokan Hilir have not been used in medicine. This study aims to determine the content of secondary metabolites and antioxidant activity in various organs of the golden banana. Simplicia powder from the golden banana organ was extracted by maceration method using 96% ethanol. The extract was then tested for antioxidant activity with a spectrophotometer using the DPPH method at a wavelength of 520 nm. The results showed that the four organs had very weak antioxidant activity. The highest antioxidant activity was in bractea with an IC50 value of 225.98 ppm and the lowest in flowers with an IC50 value of more than 1000 ppm. The results of the phytochemical screening showed that the four organs of the golden banana from Rokan downstream contained flavonoids, tannins, terpenoids, and saponins but did not contain alkaloids

Analysis of Antimicrobial Activity of Extracts From Leaves of anacardium occidentale l. (cashew) Front of Clinical Isolated from Gram-Negative Bacteria Resistant to Antibiotics

Objective: The aim of this study was to analyze the chemical composition of the hydroalcoholic extract of Anacardium occidentale L. (cashew) and the antimicrobial activity of this antibiotic against resistant gram-negative bacteria (GNB). Theoretical Framework: The spread of resistant microorganisms to available chemotherapeutic drugs is a major public health problem and points to the need for research into new antimicrobials. Plants, due to their secondary metabolism, produce compounds of biological importance, being an important source of bioprospection. Method: The collected leaves were dried at 37 °C, ground and soaked in 70% ethanol-water solution at a ratio drug / solvent of 1: 5 for seven days. After this time the mash was filtered and dried at 40 °C in a water bath until completely dry and obtain of the dry extract. The phytochemical analysis was based on the qualitative determination of saponins, alkaloids, flavonoids, steroids / triterpenoids and tannins. The study of the susceptibility of the BGN extract was determined by the technique of REMA (Resazurin Microtiter Assay), using the minimum inhibitory concentration (MIC). The maintenance of the blue or pink color in the wells of the plate was interpreted, respectively, as the presence and absence of microbial growth. Results and Discussion: Phytochemicals in trials observed the presence of saponins, flavonoids and tannins and analysis of antimicrobial activity results demonstrated weak antimicrobial activity against most of the microorganisms evaluated, except for Pseudomonas sp. (7370) that showed MIC of 250µg/mL. Research Implications: Quantitative methods are necessary to better assess and quantify the secondary metabolites of the Anacardium occidentale L. in the region.

A complete structural analysis of the FⅠ17 strike-slip fault and its hydrocarbon enrichment factors, Tarim basin, NW China

The FⅠ17 fault is a prominent strike-slip fault in the central Tarim basin, notable for its hydrocarbon abundance and intricate tectonic attributes, characterized by several deflections in its planar trajectory. Analyzing the FⅠ17 fault offers crucial insights into the role of basement structures on the evolution and formation of intracratonic strike-slip fault systems. This study utilizes the latest seismic data and integrating the foundation of previous research to conduct a detailed investigation into the spatial distribution, deformation intensity, activity phases, and formation mechanisms of the fault. The fault can be divided into three structural layers based on deformation features. The deep layer, situated beneath the TЄ3 interface (the bottom of the Upper Cambrian), shows basement rifts and weak strike-slip activity. The middle layer, spanning from TЄ3 to TO3 (the bottom of the Upper Ordovician), exhibits pronounced deformation with flower-like structures. The upper layer, extending from the TO3 to TP (the bottom of the Permian), is marked by three groups of en-echelon normal faults. Controlled by Precambrian basement heterogeneity, the fault evolved through three stages: weak compressive stress during the Middle -Late Cambrian led to rupture along basement rifts and weak zones that formed the fault’s embryonic shape; strong compressive stress from Middle-Late Ordovician activated and propagated the fault upwards; during the Silurian-Carboniferous, the fault experienced episodic reactivation and result in the emergence of en-echelon normal faults. Hydrocarbon enrichment at the FⅠ17 fault is influenced by source rock distribution, reservoir characteristics, and fault reactivation. Its positioning above the source rock center ensures an ample supply of hydrocarbon. The intense fault activity has created favorable conditions for large-scale fracture-cavity reservoir development, and the reactivation period corresponds with the hydrocarbon accumulation phase, significantly boosts hydrocarbon charging.

HPTLC-Bioautography-MS-Guided Strategy for the Detection of Phthalides With Antimicrobial and Antioxidant Activities From Ligusticum chuanxiong Essential Oil.

Antimicrobial resistance and free radical-mediated oxidative stress and inflammation involved in many pathological processes have become treatment challenges. One strategy is to search for antimicrobial and antioxidant ingredients from natural aromatic plants. This study established a rapid and high-throughput effect-component analysis method to screen active ingredients from Ligusticum chuanxiong essential oil (CXEO). The study aims to screen phthalides with antimicrobial and antioxidant activities from CXEO by high-performance thin-layer chromatography (HPTLC)-bioautography combined with HPLC-TOF/MS method. Antimicrobial activity was evaluated by disc diffusion and micro broth dilution methods. Antioxidant capacity was performed by DPPH scavenging test. Phthalides in CXEO were identified using HPLC-TOF/MS method. HPTLC-bioautography technique was established to screen phthalides of antifungal and antioxidant activities. CXEO had significant inhibitory activity against Candida albicans, weak or undetected inhibitory activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. For tested strains of C. albicans, inhibition zone diameters ranged from 13 to 17 mm, and MICs were from 0.5 to 2 mg mL-1. CXEO also had strong antioxidant activity, IC50 value for scavenging DPPH free radicals was 1.014 ± 0.014 mg mL-1. Nine phthalides in CXEO were tentatively identified. Ligustilide and senkyunolide A were screened to have both antimicrobial activity against C. albicans and strong DPPH scavenging property. HPTLC-bioautography-MS-guided strategy is very practical for high-throughput screening of antifungal and antioxidant phthalides from CXEO. Invitro experiments have shown that phthalides and CXEO have good biological activities, which may be used to the treatment of C. albicans infection or oxidative stress damage caused by various diseases. The therapeutic potential should be validated invivo in the future.

Bioactive Steroids with Structural Diversity from the South China Sea Soft Coral Lobophytum sp. and Sponge Xestospongia sp.

A chemical investigation of the soft coral Lobophytum sp. and the sponge Xestospongia sp. from the South China Sea led to the isolation of five steroids, including two new compounds (1 and 4) and one known natural product (3). Compounds 1-3 were derived from the soft coral Lobophytum sp., while 4 and 5 were obtained from the sponge Xestospongia sp. The structures of these compounds were determined by extensive spectroscopic analysis, the time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculation method, and comparison with the spectral data previously reported in the literature. The antibacterial and anti-inflammatory activities of isolated compounds were evaluated in vitro. Compounds 1-3, 4, and 5 exhibited weak antibacterial activity against vancomycin-resistant Enterococcus faecium G1, Streptococcus parauberis KSP28, Photobacterium damselae FP2244, Lactococcus garvieae FP5245, and Pseudomonas aeruginosa ZJ028. Moreover, compound 3 showed significant anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells, with an IC50 value of 13.48 μM.

Synthesis and antimicrobial activity of functionally substituted 1,3-dioxacycloalkanes

One of the directions in the development of organic chemistry is the synthesis of biologically active compounds, including those with bactericidal activity, based on available petrochemical raw materials. In order to expand the library of bioactive compounds containing a 1,3-dioxacyclane fragment, the synthesis of derivatives of 5-acyl-5-isopropyl-1,3-dioxane – 1-(5-isopropyl-1,3-dioxane-5-yl)ethanol and (5-isopropyl-1,3-dioxane-5-yl)ethyl phenyl carbamate was carried out. The effect of synthesized compounds containing a 1,3-dioxacyclane fragment on the growth of strains of gram-negative and gram-positive bacteria, lower fungi Candida albicans was studied. It was found that 2-methyl-2-ethyl-4-chloromethyl-1,3-dioxolane, containing a chloromethyl group, has an antimicrobial effect against gram-positive and gram-negative test cultures and weak antifungal activity (minimum inhibitory concentration is 100 μg/mL) against lower fungi Candida albicans. 1-(5-Isopropyl-1,3-dioxan-5-yl)ethanol exhibits antifungal activity (minimum inhibitory concentration is 2 μg/mL) and sharply reduces antimicrobial activity against Klebsiella pneumonia, Staphylococcus aureus, Enterobacter aerogenes (minimum inhibitory concentration is 100 μg/mL), in contrast to the structurally similar 2-methyl-2-ethyl-4-hydroxymethyl-1,3-dioxolane, which did not show similar properties. 5-Acyl-5-isopropyl-1,3-dioxane, containing a carbonyl group in its structure, showed antimicrobial activity (minimum inhibitory concentration is 25 μg/mL) against gram-negative test cultures, with the exception of Pseudomonas aeruginosa. Heterocycles (2-methyl-2-ethyl-4-chloromethyl-, 2-isobutyl-2,4-dimethyl-, 2-methyl-2-isobutyl-4-chloromethyl- and 2-methyl-2-isobutyl-4-hydroxymethyl-1,3-dioxolane) at concentrations up to 100 μg/mL did not inhibit the vital activity of the studied bacteria and lower fungi. The results obtained show the prospect of continuing the search for new antimicrobial and antifungal drugs of the series of 1,3-dioxacycloalkanes, the structure of which is fundamentally different from the known antibacterial drugs.

Studying the Oncolytic Activity of Streptococcus pyogenes Strains Against Hepatoma, Glioma, and Pancreatic Cancer In Vitro and In Vivo.

Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic potential of Group A Streptococcus (GAS) strains for tumor treatment. This study aimed to investigate the oncolytic efficacy of S. pyogenes GUR and its M protein knockout mutant, S. pyogenes strain GURSA1, which was genetically constructed to minimize overall toxicity, against mouse hepatoma 22A, pancreatic cancer PANC02, and human glioma U251 cells, both in vitro and in vivo, using the C57BL/6 mouse model. The in vitro oncolytic cytotoxic activity of GAS strains was studied against human glioma U251, pancreatic cancer PANC02, murine hepatoma 22a, and normal skin fibroblast cells using the MTT assay and the real-time xCELLigence system. A syngeneic mouse model of hepatoma and pancreatic cancer was used to evaluate the in vivo oncolytic effect of GAS strains. Statistical analysis was conducted using Student's t-test and Mann-Whitney U-test with GraphPad Prism software. The in vitro model showed that the live S. pyogenes GUR strain had a strong cytotoxic effect (67.4 ± 1.9%) against pancreatic cancer PANC02 cells. This strain exhibited moderate (38.0 ± 1.8%) and weak (16.3 ± 5.4%) oncolytic activities against glioma and hepatoma cells, respectively. In contrast, the S. pyogenes GURSA1 strain demonstrated strong (86.5 ± 1.6%) and moderate (36.5 ± 1.8%) oncolytic activities against glioma and hepatoma cells. Additionally, the S. pyogenes GURSA1 strain did not exhibit cytotoxic activity against healthy skin fibroblast cells (cell viability 104.2 ± 1.3%, p = 0.2542). We demonstrated that tumor treatment with S. pyogenes GURSA1 significantly increased the lifespan of C57BL/6 mice with hepatoma (34 days, p = 0.040) and pancreatic cancer (32 days, p = 0.039) relative to the control groups (24 and 28 days, respectively). Increased lifespan was accompanied by a slowdown in tumor progression, as evidenced by a reduction in the growth of hepatoma and pancreatic cancer tumors under treatment with GAS strains in mice. Both S. pyogenes GUR and S. pyogenes GURSA1 strains demonstrated strong oncolytic activity against murine hepatoma 22a, pancreatic cancer PANC02, and human U251 glioma cells in vitro. In contrast, S. pyogenes GUR and GURSA1 did not show toxicity against human normal skin fibroblasts. The overall survival rate and lifespan of mice treated with S. pyogenes GURSA1, a strain lacking the M protein on its surface, were significantly higher compared to the control and S. pyogenes GUR strain groups.

Flavonoid glycosides in Lepidium sativum seeds and their bioactivities.

Twelve flavonoid glycosides including five undescribed ones, lepisativutimines Q-U, were isolated and identified from Lepidium sativum seeds. Acid hydrolysis followed by acetic derivatization and GC analysis were conducted to determine the absolute configurations for sugars. Lepisativutimine U and beitingxinhuangtong A were uncommon kaempferol 8-S-glycosides, and complete NMR data of beitingxinhuangtong A were provided for the first time. Mass fragmentation pathways of isolated compounds were deduced based on their MS/MS data, and characteristic mass fragmentation patterns were summarized. Lepisativutimine U and kaempferol-7-O-α-l-rhamnopyranoside exhibited weak anti-diabetic activity against PTP1B with IC50 values of 60.58 ± 3.53 and 33.90 ± 2.89 μM, respectively, quercetin-7-O-α-l-rhamnopyranoside displayed significant anti-diabetic activity against α-glucosidase with an IC50 value of 25.96 ± 0.30 μM, and kaempferol 3-O-β-d-glucopyranosyl-(1→2)-β-d-galactopyranoside-7-O-α-l-rhamnopyranoside and kaempferol-7-O-α-l-rhamnopyranoside showed weak inhibitory activity against NO release in LPS-induced RAW264.7 cells with IC50 values of 92.28 ± 4.19 and 40.77 ± 1.50 μM, respectively.

Astaxanthin demonstrates moderate or weak activity against bacterial and fungal pathogens

Astaxanthin demonstrates moderate or weak activity against bacterial and fungal pathogens

New C-linked diarylheptanoid dimers as potential α-glucosidase inhibitors evidenced by biological, spectral and theoretical approaches.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, generally due to defects of insulin action or secretion. Inhibition of α-glucosidase, an enzyme responsible for carbohydrate degradation, is a promising strategy for managing postprandial hyperglycemia in diabetic patients. In this study, two new C-linked diarylheptanoid dimers, kaemgalanganols A (1) and B (2), were isolated from K. galanga, which showed obvious inhibitory activity on α-glucosidase but weak activity on protein tyrosine phosphatase 1B (PTP1B). Kaemgalanganol B had an IC50 value of 35.1μM against α-glucosidase, obviously more potent than kaemgalanganol A (IC50=78.5μM) and acarbose (IC50=363.0μM). Enzyme kinetic study indicated that 2 was a reversible mixed-type inhibitor of α-glucosidase via non-competitive and anti-competitive inhibition modes. Fluorescence quenching and UV-visible spectroscopic study revealed that fluorescence quenching mechanism of 2 on α-glucosidase is a combination of dynamic quenching and static quenching, accompanied by non-radiative energy transfer. Compound 2 formed complex with α-glucosidase closer to the Tyr residue, and induced changes in both the microenvironment and peptide backbone. Surface hydrophobicity and CD spectra measurement indicated that 2 affected the function of α-glucosidase by decreasing the surface hydrophobicity of α-glucosidase as well as altering the secondary structure instead of the overall three-dimensional framework, which is consistent with the results of fluorescence experiment. Molecular docking manifested that compound 2 had a strong binding affinity (-7.27kcal/mol) with α-glucosidase, higher than 1 (-9.82kcal/mol) and acarbose (-4.48kcal/mol), consistent with the enzyme inhibitory assay. Besides hydrogen bonds, electrostatic interactions and hydrophobic interactions played important roles in the binding of 2 with α-glucosidase. This study disclosed the inhibitory activity and mechanism of 2 against α-glucosidase, which provides a theoretical basis for the development of new antidiabetic drugs form K. galanga.

ANTIOXIDANT AND In-vitro CYTOTOXIC ACTIVITY OF TYPICAL ACEHNESE PLANTS AGAINST HUMAN CERVICAL CANCER (HeLa) CELL LINE AND THEIR PHYTOCHEMICAL PROPERTIES

Michelia Alba (M. Alba) plant is one of the typical Acehnese plants that has a lot of bioactivity and potential as a basic ingredient for drug manufacture. The aim of this study was to determine the phytochemical properties, antioxidant and in vitro cytotoxic activity of M. Alba leaves and flowers against the human cervical cancer (HeLa) cell line. This research was conducted by maceration method, where dry samples were soaked with ethanol solvents, and then crude ethanol extract was tested for antioxidant and in vitro cytotoxic activity against the HeLa cell line. The results of phytochemical properties showed leaves and flowers of M. alba contained secondary metabolites including alkaloids, terpenoids, flavonoids, tannins, and saponins. Antioxidant testing using DPPH solution of M. alba leaves showed IC50 value was 81.99 and for flowers was 30.18, this result indicates that M. alba flowers have very strong antioxidant activity, while the leaves have weak activity. The results of the cytotoxic test on the HeLa cell line from M. alba leaves and flowers showed very active where the CD50 values were 4 ppm and 2 ppm, respectively.

Deep dive into the diversity and properties of rhodopsins in actinomycetes of the family Geodermatophilaceae.

In recent decades, most studies of microbial rhodopsins have focused on their identification and characterization in aquatic bacteria. In 2021, actinomycetes of the family Geodermatophilaceae, commonly inhabiting terrestrial ecosystems in hot and arid regions, have been reported to contain rhodopsins with DTEW, DTEF and NDQ amino acid motifs. An advanced bioinformatics analysis performed in this work additionally revealed NTQ rhodopsin and heliorhodopsins. The absorption maxima identified for rhodopsins from the above five groups ranged from 513nm (NTQ rhodopsin) to 559nm (heliorhodopsin). An assessment of pumping specificity showed that DTEW and DTEF rhodopsins possessed outward H+-transport activities. Ca2+ ions were required for pumping if E. coli C43(DE3) was used as an expression strain, but were unnecessary in the case of E. coli BL21(DE3). For NDQ rhodopsin, outward H+-transport was detected in NaCl and KCl solutions at pH5 and 6, but not at neutral pH. A weak Na+-efflux was observed for this rhodopsin at pH6 and 7 in a NaCl solution only in the presence of proton ionophore. NTQ rhodopsin acted as an inward Cl--, Br--, and I-- pump, with a much weaker activity towards NO3-. No pumping activity was detected for the heliorhodopsin tested. The finding of rhodopsins with novel properties further expands the rhodopsin landscape.

Effect of extraction method on antioxidant activity and phytochemical content of purple okra extract supplements

This study analyzed the effects of extraction methods on the antioxidant activity and phytocemical content of purple okra extract supplements. The extraction methods used in the preparation of the supplements were maceration and digestion. The purple okra extract supplement showed antioxidant capacity expressed as % inhibition of 99.73±0.17% and 83.46±0.90%, with an AEAC of 12.50±0.32 and 9.43±0.17 mg AEAC g⁻¹. The antioxidant activity, expressed as IC50, was measured at 233.01±61.69 and 391.05±8.90 ppm, indicating weak antioxidant activity. The purple okra extract supplement showed total phenols of 72.80±18.55 and 62.65±22.85 mg GAE g⁻¹, and total flavonoid content of 90.73±6.11 and 75.62±7.06 mg QE g⁻¹. Based on the statistical analysis using an independent t-test, it was found that the extraction method significantly affected the parameters of antioxidant activity and capacity, as well as total flavonoid content. By elucidating the influence of extraction methods on the activity, capacity, and phytochemical content of purple okra extract supplements, this study enhances our understanding of the importance of using appropriate extraction methods to maximize the extraction of active compounds. Future research is expected to optimize extraction methods, exploring solvent combinations, conducting in vivo studies on the therapeutic potential of purple okra, and examining its molecular mechanisms.

Three new diterpenes from the roots of Salvia miltiorrhiza and their cytotoxicity.

Two undescribed oxazole-containing diterpenoids (1-2) and a new diterpenoid (3) were isolated from the roots of Salvia miltiorrhiza. Their structures were elucidated by extensive HRESIMS and NMR spectroscopic analysis, and the absolute configurations of 1 and 3 were confirmed by comparison of the calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 represents the first example of an abietane diterpenoid with a benzo[d]oxazole unit fused in the ring B of the abietane skeleton. The cytotoxicity of 1-3 was evaluated against four human tumor cell lines (A549, MCF-7, HepG2, and PC-3), and 1-2 showed weak cytotoxic activities.