Cosmetic Preservative Potential and Chemical Composition of Lafoensia replicata Pohl. Leaves.

The study evaluated the preservative potential of Lafoensia replicata Pohl. leaf extracts in cosmetics, highlighting their antioxidant, antimicrobial, and in vitro cytotoxic activities for ethanolic extract prepared by the maceration and tincture method. Total phenol content showed a higher phenol concentration in ethanolic extract and tinctures, and by LC-MS/MS-ESI-QTOF analysis, flavonoids, hydrolyzed tannins, and phenolic acids were identified. The ethanolic extract and tincture showed high antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans (MIC < 50 µg mL-1), high antioxidant activity (EC50 < 50 µg mL-1 in the DPPH method, and results > 450 µmol trolox equivalent in the ABTS and FRAP method), and low cytotoxicity in human keratinocytes (IC50 > 350 µg mL-1). The results suggest these extracts could be an alternative to synthetic preservatives in the cosmetic industry.

Synthesis of Para-Acetylated Functionalized Ni(II)-POCOP Pincer Complexes and Their Cytotoxicity Evaluation Against Human Cancer Cell Lines.

A series of three Ni(II)-POCOP complexes para-functionalized with an acetoxyl fragment were synthesized. All complexes (2 a-c) were fully characterized through standard analytical techniques. The molecular structure of complex 2 b was unambiguously determined by single-crystal X-ray diffraction, revealing that the metal center is situated in a slightly distorted square-planar environment. Additionally, the acetoxy fragment at the para-position of the phenyl ring was found to be present. The in vitro cytotoxic activity of all complexes was assessed on six human cancer cell lines. Notably, complex 2 b exhibited selective activity against K-562 (chronic myelogenous leukemia) and MCF-7 (mammary adenocarcinoma) with IC50 values of 7.32±0.60 µM and 14.36±0.02 µM, respectively. Furthermore, this compound showed negligible activity on the healthy cell line COS-7, highlighting the potential therapeutic application of 2 b. The cytotoxic evaluations were further complemented with molecular docking calculations to explore the potential biological targets of complex 2 b, revealing interactions with cluster differentiation protein 1a (CD1 A, PDB: 1xz0) for K-562 and with the progesterone receptor for MCF-7.

New Chalcone Ester Derivatives as Potential Cytotoxic Agents.

Chalcones are a group of molecules with recognized biological potential against many diseases, including cancer. Thus, studies on this structure and derivatives have become an attractive chemical strategy to optimize their observed biological activities. One of the synthetic routes used to obtain chalcone derivatives is esterification using either commercial acid chlorides or carboxylic acids. This work focuses on preparing chalcone derivatives and investigating their biological potential against cancer cells. Compound 3'-hydroxychalcone (1) was synthetized by Claisen-Schmidt condensation followed by esterification of the 3'-OH, resulting in eight compounds named 1a-b and 2a-f. All structures were confirmed by 1H and 13C NMR and FT-IR, and cytotoxicity was evaluated in the HCT 116 (colon adenocarcinoma), MCF-7 (breast adenocarcinoma), and CCD-18Co (nontumoral colon fibroblasts) cell lines. Chalcone derivatives were generally more active toward the colon cancer cell line, and 1a and 2b were selected for IC50 determination, presenting IC50 values of approximately 10 µM in HCT 116 cells and above 20 µM in both MCF7 and CDC-18-Co cells, suggesting moderate selectivity. Additionally, we tested compounds 1a and 2b in combination with doxorubicin, but they did not act synergistically with this anthracycline. In conclusion, considering these compounds obtained by the esterification reaction, 1a and 2d showed better results against cytotoxic cells.

Three New Polyprenylated Benzophenone Derivatives Isolated from Clusia burle-marxii.

Three new polyprenylated benzophenone derivatives named burlemarxione G-I (1-3) were isolated from C. burle-marxii trunks (compound 1) and leaves (compounds 2 and 3), along with the known compound burlemarxione F. Burlemarxione G (1) was isolated after methylation with diazomethane and it is the keto-enol tautomeric pair of burlemarxione F. Burlemarxione H (2) derives from burlemarxiones F and G, but it has additional rings due to cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. Burlemarxione I (3) has two additional cyclizations: the first encompasses the cyclization of the former isopentenyl group into an 11,11-dimethyl-six-membered ring, whereas the second produces additional rings due to the cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. All three compounds showed moderate anti-glioma activity. These results show that C. burle-marxii is an important source of sophisticated polyprenylated benzophenone derivatives.

Uncovering Metabolic Alterations in HCT-116 Colon Cancer Cells upon Exposure to Bamboo Leaf Extract Obtained from Guadua incana Londoño.

Metabolic alterations are increasingly recognized as important aspects of colorectal cancer (CRC), offering potential avenues for identifying therapeutic targets. Previous studies have demonstrated the cytotoxic potential of bamboo leaf extract obtained from Guadua incana (BLEGI) against HCT-116 colon cancer cells. However, the altered metabolic pathways in these tumor cells remain unknown. Therefore, this study aimed to employ an untargeted metabolomic approach to reveal the metabolic alterations of the endometabolome and exometabolome of HCT-116 cells upon exposure to BLEGI treatment. First, a chemical characterization of the BLEGI was conducted through liquid chromatography coupled with mass spectrometry (LC-MS). Next, we assessed cell viability via MTT and morphological analysis using an immunofluorescence assay against colon cancer cells, and anti-inflammatory activity using an LPS-stimulated macrophage model. Subsequently, we employed LC-MS and proton nuclear magnetic resonance (1H-NMR) to investigate intra- and extracellular changes. Chemical characterization primarily revealed the presence of compounds with a flavone glycoside scaffold. Immunofluorescence analysis showed condensed chromatin and subsequent formation of apoptotic bodies, suggesting cell death by apoptosis. The results of the metabolomic analysis showed 98 differential metabolites, involved in glutathione, tricarboxylic acid cycle, and lipoic acid metabolism, among others. Additionally, BLEGI demonstrated significant nitric oxide (NO) inhibitory capacity in macrophage cells. This study enhances our understanding of BLEGI's possible mechanism of action and provides fresh insights into therapeutic targets for treating this disease.

Indium(III) complexes with lapachol: cytotoxic effects against human breast tumor cells and interactions with DNA.

Lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione) is a 1,4-naphthoquinone-derived natural product that presents numerous bioactivities and was shown to have cytotoxic effects against several human tumor cells. Indium(III) complexes with a variety of ligands also exhibit antineoplastic activity. Indium(III) complexes [In(lap)Cl2].4H2O (1), [In(lap)2Cl(Et3N)] (2), [In(lap)3]·2H2O (3) [In(lap)(bipy)Cl2] bipy = 2,2'-bipyridine (4) and [In(lap)(phen)Cl2] phen = 1,10-phenanthroline (5) were obtained with 2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione (lapachol). Crystal structure determinations for (4) and (5) revealed that the indium(III) center is coordinated to two O atoms from lapachol, two N atoms from 1,10-phenanthroline or 2,2'-bipyridine, and two chloride anions, in a distorted octahedral geometry. Although both complexes (4) and (5) interacted with CT-DNA in vitro by an intercalative mode, only 5 exhibited cytotoxicity against MCF-7 and MDA-MB breast tumor cells. 1,10-phenanthroline and complex (5) presented cytotoxic effects against MCF-7 and MDA-MB cells, with complex (5) being threefold more active than 1,10-phenanthroline on MCF-7 cells. In addition, complex (5) significantly reduced the formation of MDA-MB-231 colonies in a clonogenicity assay. The foregoing results suggest that further studies on the cytotoxic effects and cellular targets of complex (5) are of utmost relevance.

Ethanolic Extract from Fruits of Pintoa chilensis, a Chilean Extremophile Plant. Assessment of Antioxidant Activity and In Vitro Cytotoxicity.

Pintoa chilensis is a shrub with yellow flowers that reach up to two meters high, endemic of the Atacama Region in Chile. This species grows under special environmental conditions such as low altitude, arid areas, and directly sun-exposed habitats. In the present study, ethanolic extract was obtained from fruits of P. chilensis, and then partitioned in solvents of increasing polarity to obtain five fractions: hexane (HF), dichloromethane (DF), ethyl acetate (AF), and the residual water fraction (QF). The antioxidant activity of extracts was evaluated by using the DPPH, ABTS, and FRAP methods. The results show that the antioxidant capacity of P. chilensis is higher than that reported for other plants growing in similar environments. This effect is attributed to the highest content of flavonoids and total phenols found in P. chilensis. On the other hand, the cell viability of a breast cancer cell line (MCF-7) and a non-tumor cell line (MCF-10A) was assessed in the presence of different extract fractions. The results indicate that the hexane fraction (HF) exhibits the highest cytotoxicity on both cell lines (IC50 values equal to 35 and 45 µg/mL), whereas the dichloromethane fraction (DF) is the most selective one. The GC-MS analysis of the dichloromethane fraction (DF) shows the presence of fatty acids, sugars, and polyols as major components.

Advancing molecular modeling and reverse vaccinology in broad-spectrum yellow fever virus vaccine development.

Yellow fever outbreaks are prevalent, particularly in endemic regions. Given the lack of an established treatment for this disease, significant attention has been directed toward managing this arbovirus. In response, we developed a multiepitope vaccine designed to elicit an immune response, utilizing advanced immunoinformatic and molecular modeling techniques. To achieve this, we predicted B- and T-cell epitopes using the sequences from all structural (E, prM, and C) and nonstructural proteins of 196 YFV strains. Through comprehensive analysis, we identified 10 cytotoxic T-lymphocyte (CTL) and 5T-helper (Th) epitopes that exhibited overlap with B-lymphocyte epitopes. These epitopes were further evaluated for their affinity to a wide range of human leukocyte antigen system alleles and were rigorously tested for antigenicity, immunogenicity, allergenicity, toxicity, and conservation. These epitopes were linked to an adjuvant ( ß -defensin) and to each other using ligands, resulting in a vaccine sequence with appropriate physicochemical properties. The 3D structure of this sequence was created, improved, and quality checked; then it was anchored to the Toll-like receptor. Molecular Dynamics and Quantum Mechanics/Molecular Mechanics simulations were employed to enhance the accuracy of docking calculations, with the QM portion of the simulations carried out utilizing the density functional theory formalism. Moreover, the inoculation model was able to provide an optimal codon sequence that was inserted into the pET-28a( +) vector for in silico cloning and could even stimulate highly relevant humoral and cellular immunological responses. Overall, these results suggest that the designed multi-epitope vaccine can serve as prophylaxis against the yellow fever virus.

Inclusion Complexes of Litsea cubeba (Lour.) Pers Essential Oil into ß-Cyclodextrin: Preparation, Physicochemical Characterization, Cytotoxicity and Antifungal Activity.

The uses of natural compounds, such as essential oils (EOs), are limited due to their instability to light, oxygen and temperature, factors that affect their application. Therefore, improving stability becomes necessary. The objective of this study was to prepare inclusion complexes of Litsea cubeba essential oil (LCEO) with ß-cyclodextrin (ß-CD) using physical mixing (PM), kneading (KN) and co-precipitation (CP) methods and to evaluate the efficiency of the complexes and their physicochemical properties using ATR-FTIR, FT-Raman, DSC and TG. The study also assessed cytotoxicity against human colorectal and cervical cancer cells and antifungal activity against Aspergillus flavus and Fusarium verticillioides. The complexation efficiency results presented significant evidence of LCEO:ß-CD inclusion complex formation, with KN (83%) and CP (73%) being the best methods used in this study. All tested LCEO:ß-CD inclusion complexes exhibited toxicity to HT-29 cells. Although the cytotoxic effect was less pronounced in HeLa tumor cells, LCEO-KN was more active against Hela than non-tumor cells. LCEO-KN and LCEO-CP inclusion complexes were efficient against both toxigenic fungi, A. flavus and F. verticillioides. Therefore, the molecular inclusion of LCEO into ß-CD was successful, as well as the preliminary biological results, evidencing that the ß-CD inclusion process may be a viable alternative to facilitate and increase future applications of this EO as therapeutic medication, food additive and natural antifungal agent.

Alliaxylines A-E: five new mexicanolides from the stem barks of Dysoxylum alliaceum (Blume) Blume ex A.Juss.

A total of five new mexicanolides (1-5), namely alliaxylines A-E, together with two known limonoids 6 and 7, were isolated and identified from Dysoxylum alliaceum (Blume) Blume ex. A.Juss. (Meliaceae). The structures of these compounds were elucidated based on extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D, and 2D NMR, as well as theoretical stimulation of NMR shifts with the DP4 + algorithm. Consequently, this study aimed to examine cytotoxic activities of these compounds against MCF-7 and A549 cell lines. The results implied that compound 2 was the most potent against the two tested cells, with IC50 values of 34.95 ± 0.21 and 44.39 ± 1.03 µM.

Article review: Brazilin as potential anticancer agent.

Brazilin is the main compound in Caesalpinia sappan and Haematoxylum braziletto, which is identified as a homoisoflavonoid based on its molecular structure. These plants are traditionally used as an anti-inflammatory to treat fever, hemorrhage, rheumatism, skin problems, diabetes, and cardiovascular diseases. Recently, brazilin has increased its interest in cancer studies. Several findings have shown that brazilin has cytotoxic effects on colorectal cancer, breast cancer, lung cancer, multiple myeloma, osteosarcoma, cervical cancer, bladder carcinoma, also other cancers, along with numerous facts about its possible mechanisms that will be discussed. Besides its flavonoid content, brazilin is able to chelate metal ions. A study has proved that brazilin could be used as an antituberculosis agent based on its ability to chelate iron. This possible iron-chelating of brazilin and all the studies discussed in this review will lead us to the statement that, in the future, brazilin has the potency to be a chemo-preventive and anticancer agent. The article review aimed to determine the brazilin mechanism and pathogenesis of cancer.

Anti-migratory and cytotoxic effect of indole derivative in C6 glioma cells.

Gliomas are among the most common primary malignant brain tumors. Despite advances in cancer treatment, survival is very low, so the discovery of new therapeutic agents is essential. In this context, indole is an important source for the development of new bioactive molecules. A pharmacological screening of ten indole derivatives was carried out to evaluate the cytotoxic capacity against three tumor cell lines. After pharmacological screening, three compounds were selected, based on their high capacity to reduce cell proliferation, and their IC50 values were determined. Compound 9 exhibited the highest cytotoxic activity (IC50 = 0.4 µg/mL) in gliomas (C6 cell line), and were selected for further experiments. C6 cells were treated with compound 9 to evaluate cellular mechanisms such as colony formation and cell migration capacity and morphological alterations. Compound 9 decreased clone formation (0.4 and 0.8 µg/mL), and inhibited migration (0.2-0.8 µg/mL) in C6 cells. Morphological changes in cells treated with the compound 9 were also observed, such as chromatin condensation, and disorganization in cellular stress beams. Indole derivatives had a cytotoxic effect on tumor cells, and compound 9 showed the best anti-proliferative and anti-migratory activity in glioma cells.

Design of Two New Sulfur Derivatives of Perezone: In Silico Study Simulation Targeting PARP-1 and In Vitro Study Validation Using Cancer Cell Lines.

Poly-ADP-Ribose Polymerase (PARP-1) is an overexpressed enzyme in several carcinomas; consequently, the design of PARP-1 inhibitors has acquired special attention. Hence, in the present study, three compounds (8-10) were produced through a Michael addition protocol, using phenylmethanethiol, 5-fluoro-2-mercaptobenzyl alcohol, and 4-mercaptophenylacetic acid, respectively, as nucleophiles and perezone as the substrate, expecting them to be convenient candidates that inhibit PARP-1. It is convenient to note that in the first stage of the whole study, the molecular dynamics (MD) simulations and the quantum chemistry studies of four secondary metabolites, i.e., perezone (1), perezone angelate (2), hydroxyperezone (3), and hydroxyperezone monoangelate (4), were performed, to investigate their interactions in the active site of PARP-1. Complementarily, a docking study of a set of eleven sulfur derivatives of perezone (5-15) was projected to explore novel compounds, with remarkable affinity to PARP-1. The molecules 8-10 provided the most adequate results; therefore, they were evaluated in vitro to determine their activity towards PARP-1, with 9 having the best IC50 (0.317 µM) value. Additionally, theoretical calculations were carried out using the density functional theory (DFT) with the hybrid method B3LYP with a set of base functions 6-311++G(d,p), and the reactivity properties were compared between the natural derivatives of perezone and the three synthesized compounds, and the obtained results exhibited that 9 has the best properties to bind with PARP-1. Finally, it is important to mention that 9 displays significant inhibitory activity against MDA-MB-231 and MCF-7 cells, i.e., 145.01 and 83.17 µM, respectively.

Effects of the tetravanadate [V4O12]4- anion on the structural, magnetic, and biological properties of copper/phenanthroline complexes.

The aim to access linked tetravanadate [V4O12]4- anion with mixed copper(II) complexes, using α-amino acids and phenanthroline-derived ligands, resulted in the formation of four copper(II) complexes [Cu(dmb)(Gly)(OH2)]2[Cu(dmb)(Gly)]2[V4O12]·9H2O (1) [Cu(dmb)(Lys)]2[V4O12]·8H2O (2), [Cu(dmp)2][V4O12]·C2H5OH·11H2O (3), and [Cu(dmp)(Gly)Cl]·2H2O (4), where dmb = 4,4'-dimethioxy-2,2'-bipyridine; Gly = glycine; Lys = lysine; and dmp = 2,9-dimethyl-1,10-phenanthroline. The [V4O12]4- anion is functionalized with mixed copper(II) units in 1 and 2; while in 3, it acts as a counterion of two [Cu(dmp)]2+ units. Compound 4 crystallized as a unit that did not incorporate the vanadium cluster. All compounds present magnetic couplings arising from Cu⋯O/Cu⋯Cu bridges. Stability studies of water-soluble 3 and 4 by UV-Vis spectroscopy in cell culture medium confirmed the robustness of 3, while 4 appears to undergo ligand scrambling over time, resulting partially in the stable species [Cu(dmp)2]+ that was also identified by electrospray ionization mass spectrometry at m/z = 479. The in vitro cytotoxicity activity of 3 and 4 was determined in six cancer cell lines; the healthy cell line COS-7 was also included for comparative purposes. MCF-7 cells were more sensitive to compound 3 with an IC50 value of 12 ± 1.2 nmol. The tested compounds did not show lipid peroxidation in the TBARS assay, ruling out a mechanism of action via reactive oxygen species formation. Both compounds inhibited cell migration at 5 µM in wound-healing assays using MCF-7, PC-3, and SKLU-1 cell lines, opening a new window to study the anti-metastatic effect of mixed vanadium-copper(II) systems.

Anti-biofilm and anti-inflammatory active diterpene isolated from the fruit of Xylopia benthamii R.E.Fr.

Xylopia benthamii (Annonaceae) is a plant with limited phytochemical and pharmacological evidence. Thus, using LC-MS/MS, we performed exploratory analyses of the fruit extract of X. benthamii, resulting in the tentative identification of alkaloids (1-7) and diterpenes (8-13). Through the application of chromatography techniques with the extract of X. benthamii, two kaurane diterpenes were isolated, xylopinic acid (9) and ent-15-oxo-kaur-16-en-19-oic acid (11). Their structures were established using spectroscopy (NMR 1D/2D) and mass spectrometry. The isolated compounds were submitted to anti-biofilm analysis against Acinetobacter baumannii, anti-neuroinflammatory and cytotoxic activity in BV-2 cells. Compound 11 (201.75 µM) inhibited 35% of bacterial biofilm formation and high anti-inflammatory activity in BV-2 (IC50 = 0.78 µM). In conclusion, the results demonstrated that compound 11 was characterized for the first time with pharmacological potential in the development of new alternatives for studies with neuroinflammatory diseases.

The features and management of acquired resistance to PD1-based therapy in metastatic melanoma.

BACKGROUND: Anti-PD-1 therapy (PD1) either alone or with anti-CTLA-4 (CTLA4), has high initial response rates, however 20% of patients (pts) with complete response (CR) and 30% with partial response (PR) within 12 months of treatment experience subsequent disease progression by 6 years. The nature and optimal management of this acquired resistance (AR) remains unknown. METHODS: Pts from 16 centres who responded to PD1-based therapy and who later progressed were examined. Demographics, disease characteristics and subsequent treatments were evaluated. RESULTS: 299 melanoma pts were identified, median age 64y, 44% BRAFV600m. 172 (58%) received PD1 alone, 114 (38%) PD1/CTLA4 and 13 (4%) PD1 and an investigational drug. 90 (30%) pts had CR, 209 (70%) PR. Median time to AR was 12.6 mo (95% CI, 11.3, 14.2). Most (N = 193, 65%) progressed in a single organ site, and in a solitary lesion (N = 151, 51%). The most frequent sites were lymph nodes (38%) and brain (25%). Management at AR included systemic therapy (ST, 45%), local therapy (LT) +ST (31%), LT alone (21%), or observation (3%). There was no statistical difference in PFS2 or OS based on management, however, PFS2 was numerically superior for pts treated with ST alone who progressed off PD1 therapy than those who progressed on PD1 (2-year PFS2 42% versus 25%, p = 0.249). mOS from AR was 38.0 months (95% CI, 29.5-NR); longer in single-site versus multi-site progression (2-year OS 70% vs 54%, p < 0·001). CONCLUSIONS: Acquired resistance to PD1 therapy in melanoma is largely oligometastatic, and pts may have a favorable survival outcome following salvage treatment.

GCMS characterization and biological potential of the seeds and aerial part of Galium tricorne Stokes / Caracterização GCMS e potencial biológico das sementes e parte aérea de Galium tricorne Stokes

Natural products have long been proven very effective against various challenging diseases including cancer and bacterial infections. Galium tricorne is one of the important source of natural products, which has not been explored till date in spite of its profound ethnomedicinal prominence. The current study has been designed to explore the biological potential of G. tricorne and to extract and isolate chemical constituents from its aerial part and seeds respectively along with identification of their chemical constituents. Phytochemical screening was performed to figure out the presence of secondary metabolite in G. tricorne. Crude Methanolic extract (Gt.Crd), which was obtained from the aerial part while the fatty acids were extracted from the seeds, which were later on analyzed by GCMS. Similarly, Well Diffusion and MTT method were used for antibacterial activity and cancer cell line assay respectively. To evaluate the cytotoxic potential, brine shrimps were used. Likewise, in Gas Chromatography-Mass Spectroscopy (GC-MS) analysis a total number of 23 compounds were identified in Gt.Crd extract out of which 7 compounds were sorted out to have some sort of toxicity profile. In the same fashion, 5 fatty acids were identified in the seeds of G. tricorne. Moreover, among the fractions, chloroform fraction (Gt.Chf) exhibited greater zone of inhibition (ZOI) 20.37 mm followed by Gt.Crd 18.40 mm against S. aureus and S. pyogenes respectively. In cytotoxicity Gt.Chf was more active followed by ethyl acetate fraction (Gt.Eta) by exhibiting 88.32±0.62% (LC50=60 µg/mL) and 73.95±2.25% (LC50=80 µg/mL) respectively at 1000 µg/mL concentration of the tested sample. Gt.Chf exhibited greater cell line inhibitory activity (IC50=61 µg/mL) against HeLa cell line. Similarly, Gt.Crd displayed IC50 values of 167.84 µg/mL and 175.46 µg/mL against HeLa and NIH/3T3 cell line respectively. Based on the literature review and screenings, it may be concluded that the aerial part and seeds of G. tricorne are the rich sources of bioactive compounds. The results of the current study also authenticate the scientific background for the ethnomedicinal uses of G. tricorne.

Os produtos naturais têm se mostrado muito eficazes contra várias doenças desafiadoras, incluindo câncer e infecções bacterianas. O gálio tricorne é uma importante fonte de produtos naturais, ainda pouco explorada, apesar de sua profunda proeminência etnomedicinal. O presente estudo foi desenvolvido para explorar o potencial biológico de G. tricorne e extrair e isolar constituintes químicos de sua parte aérea e sementes, respectivamente, juntamente com a identificação de seus constituintes químicos. A triagem fitoquímica foi realizada para descobrir a presença de metabólito secundário em G. tricorne, extrato metanólico bruto (Gt.Crd) que foi obtido da parte aérea enquanto os ácidos graxos foram extraídos das sementes, que posteriormente foram analisadas por GCMS. Da mesma forma, os métodos Well Diffusion e MTT foram usados ​​para atividade antibacteriana e ensaio de linha de células cancerígenas, respectivamente. Para avaliar o potencial citotóxico, foram utilizadas artémias. Da mesma forma, na análise de cromatografia gasosa-espectroscopia de massa (GC-MS) um número total de 23 compostos foi identificado no extrato de Gt.Crd, dos quais 7 compostos foram selecionados para ter algum tipo de perfil de toxicidade. Da mesma forma, 5 ácidos graxos foram identificados nas sementes de G. tricorne. Além disso, entre as frações, a fração clorofórmio (Gt.Chf) apresentou maior zona de inibição (ZOI), 20,37 mm, seguida de Gt.Crd 18,40 mm contra S. aureus e S. pyogenes, respectivamente. Na citotoxicidade Gt.Chf foi mais ativo seguido pela fração acetato de etila (Gt.Eta), exibindo 88,32±0,62% (LC50=60 µg/mL) e 73,95±2,25% (LC50=80 µg/mL) respectivamente a 1000 µg/ concentração de mL da amostra testada. Gt.Chf exibiu maior atividade inibitória da linha celular (IC50 = 61 µg/mL) contra a linha celular HeLa. Da mesma forma, Gt.Crd apresentou valores de IC50 de 167,84 µg/mL e 175,46 µg/mL contra linha celular HeLa e NIH/3T3, respectivamente. Com base na revisão de literatura e triagens, pode-se concluir que a parte aérea e as sementes de G. tricorne são as ricas fontes de compostos bioativos. Os resultados do presente estudo também autenticam a base científica para os usos etnomedicinais de G. tricorne.

Phytochemistry, allelopathy and anticancer potentiality of Withania somnifera (L. ) Dunal (Solanaceae) / Fitoquímica, alelopatia e potencialidade anticancerígena de Withania somnifera (L. ) Dunal (Solanaceae)

Withania somnifera is a wild plant that shows great activity and safety against several human diseases. The current research explored the plant's chemical composition and allelopathic effects on Rumex dentatus (recipient plant). Moreover, anticancer activity is also tested against four types of human cancer cell lines. Chemical analysis of W. somnifera showed a high percentage of saponins and tannins, while glycosides, alkaloids, and flavonoids occurred in the second order. Results of the allelopathic experiments revealed significant inhibition of the R. dentatus plumule and radicle lengths as well as their relative dry weights. In addition, significant reductions in some primary metabolites of R. dentatus, like non-reducing and total sugar as well as soluble proteins, were determined. Cytotoxic potentiality of W. somnifera was also proved against four different cancer lines, namely; human hepatocellular carcinoma cell line (HepG2), human non-small cell lung cancer cell line (A549), human breast cancer cell line (MCF7), and colon cancer cell line (CaCo2) with IC50 value of about 38, 19, 27, and 24 ug/ml, respectively.

Withania somnifera é uma planta silvestre que apresenta grande atividade e segurança contra diversas doenças humanas. A presente pesquisa explorou a composição química da planta e os efeitos alelopáticos em Rumex dentatus (planta receptora). Além disso, a atividade anticancerígena também é testada contra quatro tipos diferentes de linhagens de células cancerígenas humanas. A análise química de W. somnifera mostrou alta porcentagem de saponinas e taninos, enquanto glicosídeos, alcaloides, e flavonoides ocorreram na segunda ordem. Os resultados dos experimentos alelopáticos revelaram uma inibição significativa dos comprimentos de plúmula e radícula de R. dentatus, bem como seus pesos secos relativos. Além disso, foi determinada redução significativa em alguns metabólitos primários de R. dentatus como não redutores e açúcar total, bem como proteínas solúveis. A potencialidade citotóxica de W. somnifera também foi comprovada contra quatro diferentes linhas de câncer, a saber: linha celular de carcinoma hepatocelular humano (HepG2), linha celular de câncer de pulmão de células não pequenas humanas (A549), linha celular de câncer de mama humano (MCF7) e linha celular de câncer de cólon (CaCo2) com valor de IC50 de cerca de 38, 19, 27 e 24 ug/ml, respectivamente.

Cytotoxic, phytotoxic and insecticidal potential of Achillea millefolium L. and Chaerophyllum villosum wall. ex dc / Potencial citotóxico, fitotóxico e insecticida de Achillea millefolium L. e Chaerophyllum villosum

The methanolic, chloroformic and aqueous extract of Achillea millefolium and Chaerophyllum villosum were investigated for cytotoxicity, phytotoxic and insecticidal activities. Cytotoxicity was investigated by brine shrimp lethality assay indicating that the crude methanolic extract of A.millefolium and chloroformic extract of C.villosum revealed highest mortality of brine shrimps with (LD50 of 52.60 µg/ml) and (14.81 µg/ml). Phytotoxicity was evaluated using the Lemna minor bioassay which revealed that the crude methanolic extract of A.millefolium and C.villosum extract has maximum inhibition of Lemna minor with (Fl50 6.60 µg/ml) and (0.67 µg/ml).The insecticidal activity showed that among all the insects studied it was observed that methanolic extract of A. millefoliumand C. villosum was highly toxic to Sphenoptera dadkhani with (LD50=4.17 µg/ml) and (0.34 µg/ml). From the present study it can be concluded that different extracts from A. millefolium and C. villosum showed good cytotoxic, phytotoxic and insecticidal activity in a dose dependent manner.

Neste estudo, os extratos metanólico, clorofórmico e aquoso de Achillea millefolium e Chaerophyllum villosum foram analisados em relação à citotoxicidade, atividade fitotóxica e inseticida. A citotoxicidade foi analisada através do ensaio de letalidade de artémia, indicando que o extrato metanólico bruto de A. millefolium e o extrato clorofórmico de C. villosum revelaram maior mortalidade de artêmias com DL50 de 52,60 µg/ml e 14,81 µg/ml. A fitotoxicidade foi avaliada utilizando o bioensaio de Lemna minor que revelou que o extrato metanólico bruto de A. millefolium e extrato de C. villosum têm inibição máxima de Lemna minor com Fl50 6,60 µg/ml e 0,67 µg/ml. A atividade inseticida mostrou que dentre todos os insetos estudados, o extrato metanólico de A. millefolium e de C. villosum foi altamente tóxico para Sphenoptera dadkhanicom DL50 = 4,17 µg/ml e 0,34 µg/ml . Por outro lado, diferentes extratos, como A. millefolium e C. villosum apresentaram boa atividade citotóxica, fitotóxica e inseticida de forma dose-dependente.

Ligand-Based Drug Design of Genipin Derivatives with Cytotoxic Activity against HeLa Cell Line: A Structural and Theoretical Study.

Cervical cancer is a malignant neoplastic disease, mainly associated to HPV infection, with high mortality rates. Among natural products, iridoids have shown different biological activities, including cytotoxic and antitumor effects, in different cancer cell types. Geniposide and its aglycone Genipin have been assessed against different types of cancer. In this work, both iridoids were evaluated against HeLa and three different cervical cancer cell lines. Furthermore, we performed a SAR analysis incorporating 13 iridoids with a high structural similarity to Geniposide and Genipin, also tested in the HeLa cell line and at the same treatment time. Derived from this analysis, we found that the dipole moment (magnitude and direction) is key for their cytotoxic activity in the HeLa cell line. Then, we proceeded to the ligand-based design of new Genipin derivatives through a QSAR model (R2 = 87.95 and Q2 = 62.33) that incorporates different quantum mechanic molecular descriptor types (ρ, ΔPSA, ∆Polarizability2, and logS). Derived from the ligand-based design, we observed that the presence of an aldehyde or a hydroxymethyl in C4, hydroxyls in C1, C6, and C8, and the lack of the double bond in C7-C8 increased the predicted biological activity of the iridoids. Finally, ten simple iridoids (D9, D107, D35, D36, D55, D56, D58, D60, D61, and D62) are proposed as potential cytotoxic agents against the HeLa cell line based on their predicted IC50 value and electrostatic features.