Design, synthesis and biological evaluation of amphiphilic benzopyran derivatives as potent antibacterial agents against multidrug-resistant bacteria.

Antimicrobial resistance has emerged as a significant threat to global public health. To develop novel, high efficiency antibacterial alternatives to combat multidrug-resistant bacteria, A total of thirty-two novel amphiphilic benzopyran derivatives by mimicking the structure and function of antimicrobial peptides were designed and synthesized. Among them, the most promising compounds 4h and 17e displayed excellent antibacterial activity against Gram-positive bacteria (MICs = 1-4 µg/mL) with weak hemolytic activity and good membrane selectivity. Additionally, compounds 4h and 17e had rapid bactericidal properties, low resistance frequency, good plasma stability, and strong capabilities of inhibiting and eliminating bacterial biofilms. Mechanistic studies revealed that compounds 4h and 17e could effectively disrupt the integrity of bacterial cell membranes, and accompanied by an increase in intracellular reactive oxygen species and the leakage of proteins and DNA, ultimately leading to bacterial death. Notably, compound 4h exhibited comparable in vivo antibacterial potency in a mouse septicemia model infected by Staphylococcus aureus ATCC43300, as compared to vancomycin. These findings indicated that 4h might be a promising antibacterial candidate to combat antimicrobial resistance.

Ethnobotany, phytochemistry, pharmacology and quality control of Peucedanum decursivum (Miq.) Maxim: A critical review.

ETHNOPHARMACOLOGICAL RELEVANCE: Dried roots of Peucedanum decursivum, a traditional Chinese medicine (TCM), has historically respiratory diseases such as cough, thick phlegm, headache, fever, and gynecological diseases, rheumatoid arthritis, and nasopharyngeal carcinoma. AIM OF THE STUDY: Made an endeavor to evaluate the research trajectory of P. decursivum, comprehensively discern its developmental status, and offer a guideline for future investigations. MATERIALS AND METHODS: A meticulous search of literatures and books from 1955 to 2024 via databases like PubMed, Web of Science and CNKI was conducted, including topics and keywords of " P. decursivum" "Angelica decursivum" and "Zihua Qianhu". RESULTS: P. decursivum and its prescriptions have traditionally been used for treating phlegm-heat cough, wind-heat cough, gastrointestinal diseases, pain relief and so on. It contains 234 identified compounds, encompassing coumarins, terpenes, volatile oils, phenolic acids, fatty acids and derivatives. It exhibits diverse pharmacological activities, including anti-asthmatic, anti-inflammatory, antioxidant effects, anti-hypertensive, anti-diabetic, anti-Alzheimer, and anti-cancer properties, primarily attributed to coumarins. Microscopic identification, HPLC fingerprinting, and bioinformatics identification are the primary methods currently used for the quality control. CONCLUSION: P. decursivum demonstrates anti-asthmatic, anti-inflammatory, and antioxidant effects, aligning with its traditional use. However, experimental validation of its efficacy against phlegm and viruses is needed. Additionally, analgesic effects mentioned in historical texts lack modern pharmacological studies. Numerous isolated compounds exhibit highly valuable medicinal properties. Future research can delve into exploring these substances further. Rigorous of heavy metal contamination, particularly Cd and Pb, is necessary. Simultaneously, investigating its pharmacokinetics and toxicity in humans is crucial for the safety.

Synthesis of 2,2-dimethyl-chroman-based stereochemically flexible and constrained anti-breast cancer agents.

Receptors are proteinous macromolecules which remain in the apo form under normal/unliganded conditions. As the ligand approaches, there are specific stereo-chemical changes in the apo form of the receptor as per the stereochemistry of a ligand. Accordingly, a series of substituted dimethyl-chroman-based stereochemically flexible and constrained Tamoxifen analogs were synthesized as anti-breast cancer agents. The synthesized compounds 19a-e, 20a-e, 21, and 22a-e, showed significant antiproliferative activity against estrogen receptor-positive (ER+, MCF-7) and negative (ER-, MDA MB-231) cells within IC50 value 8.5-25.0 µM. Amongst all, four potential molecules viz 19b, 19e, 22a, and 22c, were evaluated for their effect on the cell division cycle and apoptosis of ER+ and ER- cancer cells (MCF-7 & MDA MB-231cells), which showed that these compounds possessed antiproliferative activity through triggering apoptosis. In-silico docking experiments elucidated the possible affinity of compounds with estrogen receptors-α and -ß.

Recent Advances and Outlook of Benzopyran Derivatives in the Discovery of Agricultural Chemicals.

Scaffold structures, new mechanisms of action, and targets present enormous challenges in the discovery of novel pesticides. The discovery of new scaffolds is the basis for the continuous development of modern agrochemicals. Identification of a good scaffold such as triazole, carbamate, methoxy acrylate, pyrazolamide, pyrido-pyrimidinone mesoionic, and bisamide often leads to the development of a new series of pesticides. In addition, pesticides with the same target, including the inhibitors of succinate dehydrogenase (SDH), oxysterol-binding-protein, and p-hydroxyphenyl pyruvate dioxygenase (HPPD), may have the same or similar scaffold structure. Recent years have witnessed significant progress in the discovery of new pesticides using natural products as scaffolds or bridges. In recent years, there have been increasing reports on the application of natural benzopyran compounds in the discovery of new pesticides, especially osthole and coumarin. A systematic and comprehensive review of benzopyran active compounds in the discovery of new agricultural chemicals is helpful to promote the discussion and development of benzopyran active compounds. Therefore, this work systematically reviewed the research and application of benzopyran derivatives in the discovery of agricultural chemicals, summarized the antiviral, herbicidal, antibacterial, fungicidal, insecticidal, nematicidal and acaricidal activities of benzopyran active compounds, and discussed the structural-activity relationship and mechanism of action. In addition, some active fragments were recommended to further optimize the chemical structure of benzopyran active compounds based on reference information.

[A new benzopyran glycoside from Gentiana macrophylla].

Thirteen compounds were isolated and identified from 70% ethanol extract of the roots of Gentiana macrophylla by multi-chromatographic methods, including microporous resin, silica gel, and C_(18) reversed-phase column chromatography, as well as HPLC as follows: macrophylloside G(1), macrophylloside D(2), 5-formyl-2,3-dihydroisocoumarin(3),(+)-medicarpin(4),(+)-syringaresinol(5), liquiritigenin(6),(3R)-sativanone(7),(3R)-3'-O-methylviolanone(8), 4,2',4'-trihydroxychalcone(9), latifolin(10), gentioxepine(11), 6α-hydroxycyclonerolidol(12), and ethyl linoleate(13). Compound 1 was a new benzopyran glycoside. Compounds 4, 6-10, 12, and 13 were isolated for the first time from Gentiana plants. Compounds 1 and 2 showed promising hepatoprotective activity against D-GalN-induced AML12 cell damage at the concentration of 10 µmol·L~(-1), and compound 2 exhibited more significant activity than silybin at the same concentration.

Design, synthesis and anticancer evaluation of some novel 7-hydroxy-4-methyl-3-substituted benzopyran-2-one derivatives.

Aim: 22 derivatives of 7-hydroxy-4-methyl-3-substituted benzopyran-2-one were designed, synthesized and evaluated for their anticancer activity. Materials & methods: The prepared compounds were screened for their cytotoxicity against the MCF-7 breast cancer cell line. The best five were then evaluated against MCF10a to check their safety and then tested for their PI3K and Akt-1 inhibitory action. The best two derivatives were further analyzed through cell cycle analysis, caspase 3/7 activation, increasing BAX level and decreasing BCL-2. Docking and absorption, distribution, metabolism and excretion prediction studies were also performed. Results & conclusion: Compounds 3b, 3c, 3j, 7 and 8 were the most active. Compounds 3c and 8 showed remarkable inhibitory action against PI3K and Akt-1 enzymes, and both are promising candidates for treatment of breast cancer.

Two undescribed benzopyran derivatives from Ranunculus sceleratus L. with their in vitro anti-inflammatory activity in lipopolysaccharide-activated RAW 264.7 cells.

Previous studies on Ranunculus sceleratus L. have shown the existence of coumarins and their anti-inflammatory effect. Phytochemical work was conducted to investigate the bioactive compounds, leading to the isolation of two undescribed benzopyran derivatives, namely ranunsceleroside A (1) and B (3), together with two known coumarins (2, 4) from the whole plant of R. sceleratus L. All compounds were structurally identified by extensive spectroscopic analysis and then investigated for their inhibitory effect on nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) production induced by lipopolysaccharide (LPS) in RAW 264.7 murine macrophages, repectively. As a result, compound 1-4 presented inhibitory effects on the production of NO, TNF-α, IL-1ß, and IL-6 in a concentration-dependent manner, which provides a potential chemical basis for the traditional use of R. sceleratus L. as an anti-inflammatory plant.

Essential Rule Derived from Thermodynamics and Kinetics Studies of Benzopyran Compounds.

Compounds with benzopyran as the core structure play an important role in the total synthesis of antioxidants, drugs, and natural products. Herein, the thermodynamic data of benzopyran compounds and their intermediates were measured and calculated by combining thermodynamics with kinetics. The mechanism of reactions between four benzopyran compounds and organic hydride acceptors was proven to be a one-step hydride transfer. The thermodynamic properties of these compounds and their corresponding intermediates were elucidated. The rationality and accuracy of the electrochemical measurement method were proved. Furthermore, the essential rule of unique structures being present between the C-H bond and para-substituent constants on the benzene ring, as shown in previous studies, was investigated. A simultaneous correlation between thermodynamics and kinetics was found for the hydride transfer reaction, in which the reaction site is connected with the substituent through the benzene ring, a double bond, or a N atom. The likely reason for the correlation between thermodynamic and kinetic is that the benzene ring, double bond, or N atom have the role of transferring the electronic effect. This finding can be applied to the calculation of the activation energy of hydride self-exchange reactions, the prediction of kinetic isotope effects, and explorations of selective reduction processes of hydride transfer in such organic hydride compounds.

Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer.

Structural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C-C bond formation was attempted in this study. The impact of substituents with varied electronic effects (phenyl ring, position 2 of the benzopyran scaffold) on the antitumor properties was also assessed. Resultantly, the efforts yielded a furyl arm bearing benzopyran possessing a 4-fluoro phenyl ring (position 2) (14) that manifested a magnificent antitumor profile against the Ishikawa cell lines mediated through dual inhibition of PARP and tubulin [(IC50 (PARP1) = 74 nM, IC50 (PARP2) = 109 nM) and tubulin (IC50 = 1.4 µM)]. Further investigations confirmed the ability of 14 to induce apoptosis as well as autophagy and cause cell cycle arrest at the G2/M phase. Overall, the outcome of the study culminated in a tractable dual PARP-tubulin inhibitor endowed with an impressive activity profile against endometrial cancer.

Synthesis of 6-alkoxy and 6-hydroxy-alkyl amine derivatives of braylin as vasorelaxing agents.

Braylin (10b) is a 8,8-dimethyl chromenocoumarin present in the plants of the family Rutaceae and Meliaceae and possesses vasorelaxing and anti-inflammatory activities. In this study, six 6-alkoxy (10b, 15-19), and twelve 6-hydroxy-alkyl amine (20a-20l) derivatives of braylin (11 and 12) were synthesized to delineate its structural requirement for vasorelaxing activity. The synthesized compounds were evaluated for vasorelaxation response in preconstricted intact rat Main Mesenteric Artery (MMA). The compounds showed l-type VDCC channel blockade depended and endothelium-independent vasorelaxation within the range of Emax < 50.00-96.70 % at 30 µM. Amongst all, 6-alkoxy derivatives were more active than 6-hydroxy-alkyl amine derivatives. The structural refinements about braylin showed that deletion of its methoxy group or homologation beyond ethoxy group presented deleterious effect on vasorelaxation response of braylin. Interestingly, substituting the ethoxy group in 10b presented the best activity and selectivity towards l-type VDCC channel blockade, a specific target cardiovascular function.

Highly selective and sensitive benzopyran-based fluorescent probes for imaging exogenous and endogenous peroxynitrite.

Peroxynitrite is widely present in organisms and closely related to many pathophysiological functions. Therefore, it is of great physiological significance to develop capable probes for detecting ONOO-. In this work, a novel fluorescent probe B-Ch was designed based on the intramolecular charge transfer (ICT) effect. By means of molecular engineering, the replacement from diethylamine group to hydroxyl group has improved the detection sensitivity of the probe. After the addition of ONOO-, the solution color and fluorescence showed noticeable changes, which were visible to the naked eye. The probe showed excellent advantages: visualization, good selectivity, low sensitivity (22.4 nM), good stability and biocompatibility, exogenous and endogenous imaging of ONOO- in HeLa cells.

Synthesis of amide derivatives of 3-aryl-3H-benzopyrans as osteogenic agent concomitant with anticancer activity.

The present study reports a series of 3-aryl-3H-benzopyran-based amide derivatives as osteogenic agents concomitant with anticancer activity. Six target compounds viz 22e, 22f, 23i, and 24b-d showed good osteogenic activity at 1 pM and 100 pM concentrations. One of the potential molecules, 24b, effectively induced ALP activity and mRNA expression of osteogenic marker genes at 1 pM and bone mineralization at 100 pM concentrations. These molecules also presented significant growth inhibition of osteosarcoma (MG63) and estrogen-dependent and -independent (MCF-7 and MDA-MB-231) breast cancer cells. The most active compound, 24b, inhibited the growth of all the cancer cells within the IC50 10.45-12.66 µM. The mechanistic studies about 24b showed that 24b induced apoptosis via activation of the Caspase-3 enzyme and inhibited cancer cell migration. In silico molecular docking performed for 24b revealed its interaction with estrogen receptor-ß (ER-ß) preferentially.

Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity.

BACKGROUND AND PURPOSE: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPARα agonists on glucose metabolism and the adverse effects associated with selective PPARγ activators have stimulated the development of novel pan-PPAR agonists to treat metabolic disorders. Here, we synthesized a new prenylated benzopyran (BP-2) and evaluated its PPAR-activating properties, anti-inflammatory effects and impact on metabolic derangements. EXPERIMENTAL APPROACH: BP-2 was used in transactivation assays to evaluate its agonism to PPARα, PPARß/δ and PPARγ. A parallel-plate flow chamber was employed to investigate its effect on TNFα-induced leukocyte-endothelium interactions. Flow cytometry and immunofluorescence were used to determine its effects on the expression of endothelial cell adhesion molecules (CAMs) and chemokines and p38-MAPK/NF-κB activation. PPARs/RXRα interactions were determined using a gene silencing approach. Analysis of its impact on metabolic abnormalities and inflammation was performed in ob/ob mice. KEY RESULTS: BP-2 displayed strong PPARα activity, with moderate and weak activity against PPARß/δ and PPARγ, respectively. In vitro, BP-2 reduced TNFα-induced endothelial ICAM-1, VCAM-1 and fractalkine/CX3CL1 expression, suppressed mononuclear cell arrest via PPARß/δ-RXRα interactions and decreased p38-MAPK/NF-κB activation. In vivo, BP-2 improved the circulating levels of glucose and triglycerides in ob/ob mice, suppressed T-lymphocyte/macrophage infiltration and proinflammatory markers in the liver and white adipose tissue, but increased the expression of the M2-like macrophage marker CD206. CONCLUSION AND IMPLICATIONS: BP-2 emerges as a novel pan-PPAR lead candidate to normalize glycemia/triglyceridemia and minimize inflammation in metabolic disorders, likely preventing the development of further cardiovascular complications.

Experimental and Theoretical Study on the Homodimerization Mechanism of 3-Acetylcoumarin.

In the present study, the reaction conditions for homodimerization process of 3-acetylcoumarin were achieved under sonication using combination of zinc and metallic salt (ZnCl2 or Zn(OAc)2). Appropriate frequency and sound amplitude have been identified as significant variables for the initiation of the reaction. On the base of first principal calculations and experimental results, the mechanism of the reaction was investigated. The relative stability of the possible intermediates has been compared, including evaluation on the ionic and radical reaction pathways for the dimerization process. Theoretical results suggested that the radical mechanism is more favorable. The C-C bond formation between the calculated radical intermediates occurs spontaneously (∆G = -214 kJ/mol for ZnCl2, -163 kJ/mol in the case of Zn(OAc)2), which proves the possibility for the homodimerization of 3-acetylcoumarin via formation of radical species. Both experimental and theoretical data clarified the activation role of the solvent on the reactivity of the Zn-salt. The formation of complexes of solvent molecules with Zn-atom from the ZnCl2 reduces the energy barrier for the dissociation of Zn-Cl bond and facilitate the formation of the dimeric product.

Design, synthesis and biological evaluation of new quinazolinone-benzopyran-indole hybrid compounds promoting osteogenesis through BMP2 upregulation.

In search of novel osteogenic entities, a series of twenty-seven quinazolinone-benzopyran-indole hybrids were designed and synthesized using molecular hybridization approach. All the compounds were scrutinized for their osteogenic potential, primarily based on alkaline phosphatase assay as one of the major anabolic markers. From the primary screening, four osteogenic compounds were sorted from the series and were found nontoxic to the osteoblasts. Further, increased osteoblast differentiation and osteogenic mRNA upregulations suggest compound 47 as the most potent osteoanabolic agent. Immunoblot and ELISA analysis demonstrated that compound 47 promotes osteogenesis via RUNX2 and BMP2 mediated non-canonical p38 pathway. In vivo studies in BALB/c mice inferred that compound 47 stimulates bone anabolism as evident from histological and gene expression studies at 5 mg. kg-1. day-1 dose. Furthermore, structural activity relationship (SAR) and pharmacokinetic studies suggest compound 47 as a BMP2 upregulator and a potential bone anabolic lead for combating future bone metabolic disorders.

Methoxylated flavones with potential therapeutic and photo-protective attributes: Theoretical investigation of substitution effect.

The molecular and electronic structure of parent flavone and 49 (poly)methoxylated flavones (P)MFs were studied theoretically. Selected group of flavonoids consists of compounds naturally occurring in citrus plants or synthetic derivatives of flavone. These compounds exhibit several bioactivities in vitro and in vivo and can protect plants from solar ultraviolet (UV) radiation. Substitution induced structural changes in (P)MFs were correlated with published experimental values of P-glycoprotein inhibition effect. We have demonstrated that the C5-C10 bond length of 1-benzopyran-4-one moiety represents a suitable structural descriptor for this bioactivity. Obtained linear equations for the compounds with substituted and non-substituted C3 position enable the prediction of the potential anti-cancer chemo-preventive effect of the rest of studied (P)MFs. Consequently, potentially more effective substances were suggested. Optical properties of (P)MFs and their relationship with the molecular structure was examined in detail for methanol environment, as well. The multiple linear regression model was applied to assess the correlation between experimental absorption and fluorescence wavelengths with the theoretically predicted ones. The UV photo-protective potential of studied derivatives was estimated from the calculated optical properties.

Effects of human induced pluripotent stem cell-derived intestinal organoids on colitis-model mice.

Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by repeated remissions and relapses. Immunosuppressive drugs have facilitated the induction and maintenance of remission in many patients with UC. However, immunosuppressive drugs cannot directly repair impaired intestinal mucosa and are insufficient for preventing relapse. Therefore, new treatment approaches to repair the damaged epithelium in UC have been attempted through the transplantation of intestinal organoids, which can be differentiated into mucosa by embedding in Matrigel, generated from patient-derived intestinal stem cells. The method, however, poses the challenge of yielding sufficient cells for UC therapy, and patient-derived cells might already have acquired pathological changes. In contrast, human induced pluripotent stem (iPS) cells generated from healthy individuals are infinitely proliferated and can be differentiated into target cells. Recently developed human iPS cell-derived intestinal organoids (HIOs) aim to generate organoids that closely resemble the adult intestine. However, no study till date has reported HIOs injected into in vivo inflammatory models, and it remains unclear whether HIOs with cells that closely resemble the adult intestine or with intestinal stem cells retain the better ability to repair tissue in colitis. Methods: We generated two types of HIOs via suspension culture with and without small-molecule compounds: HIOs that include predominantly more intestinal stem cells [HIO (A)] and those that include predominantly more intestinal epithelial and secretory cells [HIO (B)]. We examined whether the generated HIOs engrafted in vivo and compared their ability to accelerate recovery of the damaged tissue. Results: Findings showed that the HIOs expressed intestinal-specific markers such as caudal-type homeobox 2 (CDX2) and villin, and HIOs engrafted under the kidney capsules of mice. We then injected HIOs into colitis-model mice and found that the weight and clinical score of the mice injected with HIO (A) recovered earlier than that of the mice in the sham group. Further, the production of mucus and the expression of cell proliferation markers and tight junction proteins in the colon tissues of the HIO (A) group were restored to levels similar to those observed in healthy mice. However, neither HIO (A) nor HIO (B) could be engrafted into the colon. Conclusions: Effective cell therapy should directly repair tissue by engraftment at the site of injury. However, the difference in organoid property impacting the rate of tissue repair in transplantation without engraftment observed in the current study should be considered a critical consideration in the development of regenerative medicine using iPS-derived organoids.

Highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives and in silico interaction analysis with putative target Plasmodium falciparum lactate dehydrogenase.

Malaria infection caused by Plasmodium falciparum is majorly responsible for millions of deaths in humans every year. Moreover, a rapid increase in resistance to existing drugs has posed an urgent need for new anti-malarials. Herein, we report the highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives, inspired from naturally occurring dependensin against chloroquine (CQ) sensitive and resistant P. falciparum strains. Chemically synthesized, four dependensin analogs 85(A-D) exhibited growth inhibition at nanomolar concentrations ranging from 63.96 to 725.8 nM by blocking the parasite development at the ring and early trophozoite stages. The growth inhibitory activity of dependensin analogs was correlated with their anti-plasmodial lactate dehydrogenase activity by computational analysis. Molecular docking, 50 ns simulation and a 2D-Quantitative Structure-Activity Relationship (2D-QSAR) modelling revealed the interaction with their putative target P. falciparum lactate dehydrogenase (PfLDH). Here, developing the predictive 2D descriptors such as thermodynamic, spatial, electronic, and topological with multiple linear regression analysis (MLRA), the structural requirements for potent and selective PfLDH inhibitory activity has been identified. The strong binding of compound 85D to the catalytic Nicotinamide adenine dinucleotide (NADH) binding pocket of the PfLDH further supported the PfLDH targeting potential of dependensin analogs. Overall, this study revealed a highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives with their putative anti-PfLDH activity.Communicated by Ramaswamy H. Sarma.

Coumarin (2H-1-Benzopyran-2-one) act against planktonic and biofilm forms of Staphylococcus aureus, Klebsiellapneumoniae and Pseudomonas aeruginosa

SUMMARY Introduction: biofilm-related infections caused by Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa are difficult to treat and few effective pharmacological options are currently available for this purpose. In this context, coumarin (2H-1-Benzopyran-2-one) has been reported to have antibacterial and antibiofilm activity, but this potential remains poorly understood. Aim: to investigate the action of coumarin on planktonic and biofilm forms of S. aureus, K. pneumoniae and P. aeruginosa. Results: a minimum inhibitory concentration (MIC) of coumarin ranging from 256 to 1024 fig/mL was observed, with a remarkable ability to inhibit the formation of biofilms and to act on mature biofilms in concentrations close to MIC. Conclusion: coumarin has strong activity against planktonic and biofilm forms on the three species of great relevance in the clinical scenario. These results are interesting to enable a pharmacological alternative for the treatment of these infections.

Introducción: las infecciones relacionadas con la biopelícula causadas por Staphylococcus aureus, Klebsiella pneumoniae y Pseudomonas aeruginosa son difíciles de tratar y actualmente existen pocas opciones farmacológicas eficaces para este propósito. En este contexto, se ha informado que la cumarina (2H-1-Benzopiran-2-ona) tiene actividad antibacteriana y antibiofilm, pero este potencial sigue siendo poco conocido. Objetivo: investigar la acción de la cumarina sobre formas planctónicas y de biopelículas de S. aureus, K. pneumoniae y P. aeruginosa. Resultados: se observó una concentración inhibitoria mínima (CMI) de cumarina en el rango de 256 a 1024 µg/mL, con una notable capacidad para inhibir la formación de biofilms y actuar sobre biofilms maduros en concentraciones cercanas a la CMI. Conclusión: la cumarina tiene una fuerte actividad contra las formas planctónicas y biofilm sobre las tres especies de gran relevancia en el escenario clínico. Estos resultados son interesantes para habilitar una alternativa farmacológica para el tratamiento de estas infecciones.

Introdução: as infecções relacionadas ao biofilme causadas por Staphylococcus aureus, Klebsiella pneumoniae e Pseudomonas aeruginosa são difíceis de tratar e poucas opções farmacológicas eficazes estão disponíveis atualmente para esse propósito. Nesse contexto, foi relatado que a cumarina (2H-1-benzopirano-2-ona) tem atividade antibacteriana e antibiofilme, mas esse potencial permanece pouco conhecido. Objetivo: investigar a ação da cumarina sobre as formas planctónicas e de biofilme de S. aureus, K. pneumoniae e P. aeruginosa. Resultados: observou-se uma concentração inibitória mínima (CIM) de cumarina variando de 256 a 1024 µg/mL, com notável capacidade de inibir a formação de biofilmes e de atuar sobre biofilmes maduros em concentrações próximas à CIM. Conclusão: a cumarina possui forte atividade contra as formas planctónicas e de biofilme sobre as três espécies de grande relevância no cenário clínico. Esses resultados são interessantes para possibilitar uma alternativa farmacológica para o tratamento dessas infecções.

Quantitative Structure-Activity Relationships of Natural-Product-Inspired, Aminoalkyl-Substituted 1-Benzopyrans as Novel Antiplasmodial Agents.

On the basis of the finding that various aminoalkyl-substituted chromene and chromane derivatives possess strong and highly selective in vitro bioactivity against Plasmodium falciparum, the pathogen responsible for tropical malaria, we performed a structure-activity relationship study for such compounds. With structures and activity data of 52 congeneric compounds from our recent studies, we performed a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using the comparative molecular field analysis (CoMFA) approach as implemented in the Open3DQSAR software. The resulting model displayed excellent internal and good external predictive power as well as good robustness. Besides insights into the molecular interactions and structural features influencing the antiplasmodial activity, this model now provides the possibility to predict the activity of further untested compounds to guide our further synthetic efforts to develop even more potent antiplasmodial chromenes/chromanes.