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1.
RSC Adv ; 14(34): 25042-25047, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39135974

RESUMEN

Steroid groups isolated from many plants are known to play a significant role in various biological systems. Therefore, this research aimed to analyze two novel pregnane steroids, pachylenone A (1) and pachylenone B (2), isolated from Aglaia pachyphylla Miq. The cytotoxicity of the steroids was evaluated against MCF-7 breast cancer cell lines with other known steroid compounds, namely 5α-dihydroprogesterone (3), GSD-8 (4), trans-5α-pregn-l7(20)-en-3,16-dion (5), 20ß-hydroxy-5αH-pregnan-3-one (6), 3ß-hydroxy-5α-pregnan-20-one (7), aglaiasterol B (8), and 2ß,3ß-dihydroxypregnan-16-one (9). Meanwhile, structural elucidation was achieved through different spectroscopic methods including one and two-dimensional NMR, as well as mass spectroscopy and quantum chemical calculations (TD-DFT and NMR DP4+ probability). The cytotoxic effects of steroid compounds (1-9) on MCF-7 lines were also examined. The results showed that compound 8 had the strongest activity with an IC50 value of 228 µM, followed by compound 6 (IC50 568,76 µM), and pachylenone A (1) (IC50 768.73 µM). As a recommendation for future research, other activities of these compounds should be evaluated.

2.
Sci Rep ; 14(1): 15597, 2024 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971811

RESUMEN

In recent decades, the interest in natural products with immunomodulatory properties has increased due to their therapeutic potential. These products have a wider range of pharmacological activities and demonstrate lower toxicity levels when compared to their synthetic counterparts. Therefore, this study aimed to investigate the immunomodulatory effects of sesquiterpenoids (SQs) and sesquiterpenoid dimers (SQDs) isolated from Dysoxylum parasiticum (Osbeck) Kosterm. stem bark on human and murine cells, particularly focusing on toll-like receptor 4 (TLR4). Utilizing the secreted alkaline phosphatase (SEAP) assay on engineered human and murine TLR4 of HEK-Blue cells, antagonist TLR4 compounds were identified, including SQs 6, 9, and 10, as well as SQDs 17 and 22. The results showed that 10-hydroxyl-15-oxo-α-cadinol (9) had a potent ability to reduce TLR4 activation induced by LPS stimulation, with minimal toxicity observed in both human and murine cells. The SEAP assay also revealed diverse immune regulatory effects for the same ligand. For instance, SQs 12, 14, and 16 transitioned from antagonism on human to murine TLR4. The SQs (4, 7, 11, and 15) and SQDs (18-20) offered partial antagonist effect exclusively on murine TLR4. Furthermore, these selected SQs and SQDs were assessed for their influence on the production of proinflammatory cytokines TNF-α, IL-1α, IL-1ß, and IL-6 of the NF-κB signaling pathway in human and murine macrophage cell lines, showing a dose-dependent manner. Additionally, a brief discussion on the structure-activity relationship was presented.


Asunto(s)
Corteza de la Planta , Sesquiterpenos , Receptor Toll-Like 4 , Receptor Toll-Like 4/metabolismo , Humanos , Animales , Corteza de la Planta/química , Ratones , Sesquiterpenos/farmacología , Sesquiterpenos/química , Células HEK293 , Meliaceae/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , Citocinas/metabolismo , Células RAW 264.7 , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Lipopolisacáridos/farmacología
3.
RSC Adv ; 14(30): 21778-21785, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38984261

RESUMEN

The increasing prevalence of deaths due to multidrug-resistant bacteria (MDRB) in infectious disease therapy has become a global health concern. This led to the development of new antimicrobial therapeutic agents that can combat resistance to pathogenic bacteria. The utilization of natural peptide compounds as potential antimicrobial agents is very promising. Nodupetide, a cyclodepsipeptide with very strong antimicrobial activity against Pseudomonas aeruginosa was isolated from the fermentation of Nodulisporium sp. Unfortunately, one of its residues (3S,4S)-3-hydroxy-4-methylhexanoic acid (HMHA) is not commercially available and the synthesis strategies applied have not been successful. Hence, we synthesized its cyclopeptide analogue [ß-HIle]2-nodupetide by replacing HMHA with isoleucine homologue. A combination of solid- and solution-phase peptide synthesis was successfully carried out to synthesize [ß-HIle]2-nodupetide with an overall yield of 10.4%. The substitution of HMHA with ß-homoisoleucine (ß-HIle) changed the ester bond into an amide bond in nodupetide's backbone. The analogue was considerably inactive against Pseudomonas aeruginosa. It can be concluded that the ester bond is crucial for the antimicrobial activity of nodupetide.

4.
Phytochemistry ; 222: 114092, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38604323

RESUMEN

Phytochemical study of the fruits of Chisocheton erythrocarpus (Hiern) allowed the identification of eight undescribed limonoids, namely erythrocarpines O - V (1-6, 7a and 7b), along with seven known compounds. The structures of these compounds were elucidated based on spectroscopic and HRMS data, along with electronic circular dichroism to configure the absolute configuration. Erythrocarpines O and P are γ-hydroxybutenolide analogs of mexicanolide-type limonoids while erythrocarpine Q - V are phragmalin-type limonoids possessing a 1,29-oxymethylene bridge with either benzoyl or cinnamoyl moiety in their structures. Mosquito larvicidal activity revealed that crude DCM extract of C. erythrocarpus possessed a good larvicidal effect against Aedes aegypti larvae in 48 h (LC50 = 153.0 ppm). Subsequent larvicidal activity of isolated compounds indicated that erythrocarpine G (10) and 14-deoxyxyloccensin K (11) were responsible for the enhanced larvicidal effect of the extract, reporting LC50 values of 18.55 ppm and 41.16 ppm, respectively. Moreover, residual activity testing of the crude DCM extract revealed that the duration of its larvicidal effects is up to 14 days, where it maintained a 98 % larval mortality throughout the test period, under laboratory conditions.


Asunto(s)
Aedes , Frutas , Insecticidas , Larva , Limoninas , Meliaceae , Animales , Larva/efectos de los fármacos , Limoninas/farmacología , Limoninas/aislamiento & purificación , Limoninas/química , Insecticidas/farmacología , Insecticidas/química , Insecticidas/aislamiento & purificación , Frutas/química , Aedes/efectos de los fármacos , Meliaceae/química , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga
5.
J Asian Nat Prod Res ; 26(7): 843-849, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38511479

RESUMEN

A new seco-A tirucallane triterpenoid named excelxylin A (1), along with two known seco-A triterpenoids (2-3), were isolated from the n-hexane extract of Dysoxylum excelsum (Spreng.) Blume ex G.Don stem bark. The structure and stereochemistry configuration of compounds 1-3 was established by NMR, IR, and HR-ESI-MS spectroscopic data analyses and comparison of their NMR data with literatures. The compounds exhibited the carbon framework for seco-A ring tirucallane triterpenoid, first reported in the Dysoxylum genus. All compounds were tested for their cytotoxicity against human cervical HeLa cells.


Asunto(s)
Meliaceae , Corteza de la Planta , Triterpenos , Triterpenos/química , Triterpenos/farmacología , Triterpenos/aislamiento & purificación , Corteza de la Planta/química , Humanos , Estructura Molecular , Meliaceae/química , Células HeLa , Tallos de la Planta/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Resonancia Magnética Nuclear Biomolecular
6.
J Nat Med ; 78(3): 558-567, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38517622

RESUMEN

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.


Asunto(s)
Limoninas , Meliaceae , Corteza de la Planta , Humanos , Meliaceae/química , Corteza de la Planta/química , Limoninas/química , Limoninas/farmacología , Limoninas/aislamiento & purificación , Estructura Molecular , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Células MCF-7 , Células A549 , Línea Celular Tumoral , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Extractos Vegetales/farmacología , Tallos de la Planta/química
7.
RSC Adv ; 14(11): 7684-7698, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38444963

RESUMEN

New phenylisoxazole quinoxalin-2-amine hybrids 5a-i were successfully synthesised with yields of 53-85% and characterised with various spectroscopy methods. The synthesised hybrids underwent in vitro α-amylase and α-glucosidase inhibitory assays, with acarbose as the positive control. Through the biological study, compound 5h exhibits the highest α-amylase inhibitory activity with IC50 = 16.4 ± 0.1 µM while compounds 5a-c, 5e and 5h exhibit great potential as α-glucosidase inhibitors, with 5c being the most potent (IC50 = 15.2 ± 0.3 µM). Among the compounds, 5h exhibits potential as a dual inhibitor for both α-amylase (IC50 = 16.4 ± 0.1 µM) and α-glucosidase (IC50 = 31.6 ± 0.4 µM) enzymes. Through the molecular docking studies, the inhibition potential of the selected compounds is supported. Compound 5h showed important interactions with α-amylase enzyme active sites and exhibited the highest binding energy of -8.9 ± 0.10 kcal mol-1, while compound 5c exhibited the highest binding energy of -9.0 ± 0.20 kcal mol-1 by forming important interactions with the α-glucosidase enzyme active sites. The molecular dynamics study showed that the selected compounds exhibited relative stability when binding with α-amylase and α-glucosidase enzymes. Additionally, compound 5h demonstrated a similar pattern of motion and mechanism of action as the commercially available miglitol.

9.
Phytochemistry ; 220: 114009, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38342289

RESUMEN

Seven previously undescribed preurianin-type limonoids, namely paraxylines A-G, and three known analogs were isolated from stem bark of Dysoxylum parasiticum. The structures, including absolute configurations, were established through spectroscopic analyses, quantum chemical calculations using the density functional theory method, as well as the DP4+ algorithm. Paraxylines A-G were identified as the first preurianin-type with full substitution at C, D-rings, leading to the highly oxygenated seco-limonoids skeleton. The secreted alkaline phosphate assay against an engineered human and murine TLR4 of HEK-Blue cells was performed to evaluate the immune regulating effects. Among them, paraxyline B was found to be a remarkable TLR4 agonist whereas two analogs (toonapubesins A and B) were found to antagonise lipopolysaccharide stimulation of the TLR4 pathway. Paraxylines A and C-E acted either as agonists or antagonists depending on the origin of the TLR4 receptor (human or mouse). The effect of these selected compounds on the expression of pro-inflammatory cytokines TNF-α, IL-1α, IL-1ß, and IL-6 of the NF-κB signaling pathway were examined in macrophage cell lines, revealing dose-dependent effects. Additionally, paraxylines A, C, D, and G also presented modest cytotoxic activity against MCF-7 and HeLa cell lines with IC50 values ranging from 23.1 to 43.5 µM.


Asunto(s)
Antineoplásicos Fitogénicos , Antineoplásicos , Limoninas , Meliaceae , Humanos , Animales , Ratones , Limoninas/farmacología , Limoninas/química , Receptor Toll-Like 4 , Células HeLa , Corteza de la Planta/química , Estructura Molecular , Antineoplásicos Fitogénicos/química , Meliaceae/química
10.
Fitoterapia ; 174: 105873, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38417682

RESUMEN

Diabetes mellitus stands as a metabolic ailment marked by heightened blood glucose levels due to inadequate insulin secretion. The primary aims of this investigative inquiry encompassed the isolation of phytochemical components from the bark of Kopsia teoi, followed by the assessment of their α-amylase inhibition. The phytochemical composition of the K. teoi culminated in the discovery of a pair of new indole alkaloids; which are 16-epi-deacetylakuammiline N(4)-methylene chloride (akuammiline) (1), and N(1)-methoxycarbonyl-11-methoxy-12-hydroxy-Δ14-17-kopsinine (aspidofractinine) (2), together with five known compounds i.e. kopsiloscine G (aspidofractinine) (3), akuammidine (sarpagine) (4), leuconolam (aspidosperma) (5), N-methoxycarbonyl-12-methoxy-Δ16, 17-kopsinine (aspidofractinine) (6), and kopsininate (aspidofractinine) (7). All compounds were determined via spectroscopic analyses. The in vitro evaluation against α-amylase showed good inhibitory activities for compounds 5-7 with the inhibitory concentration (IC50) values of 21.7 ± 1.2, 34.1 ± 0.1, and 30.0 ± 0.8 µM, respectively compared with the reference acarbose (IC50 = 34.4 ± 0.1 µM). The molecular docking outputs underscored the binding interactions of compounds 5-7 ranging from -8.1 to -8.8 kcal/mol with the binding sites of α-amylase. Consequently, the outcomes highlighted the anti-hyperglycemic attributes of isolates from K. teoi.


Asunto(s)
Apocynaceae , Alcaloides de Triptamina Secologanina , Simulación del Acoplamiento Molecular , alfa-Amilasas , Estructura Molecular , Alcaloides Indólicos , Fitoquímicos/farmacología , Apocynaceae/química
11.
Curr Issues Mol Biol ; 46(1): 909-922, 2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38275672

RESUMEN

Chisocheton plants from the family Meliaceae have traditionally been used to treat several diseases; however, scientific evidence is limited. The most abundant chemical constituents of this plant are the limonoids, which are known for their various biological activities, including anti-inflammatory effects. However, the anti-inflammatory effects and underlying mechanisms of action of the constituents of Chisocheton plants have not been fully explored. In this report, we evaluated the anti-inflammatory activity of 17 limonoid compounds from Chisocheton plant primarily by measuring their inhibitory effects on the production of pro-inflammatory cytokines, including TNF-α, IL-6, IL-1ß, and MCP-1, in LPS-stimulated THP-1 cells using an ELISA assay. Compounds 3, 5, 9, and 14-17 exhibited significant activity in inhibiting the evaluated pro-inflammatory markers, with IC50 values less than 20 µM and a high selectivity index (SI) range. Compounds 3, 5, 9, and 15 significantly suppressed the expression of phosphorylated p38 MAPK in THP-1 cells stimulated with LPS. These findings support the use of limonoids from Chisocheton plants as promising candidates for anti-inflammatory therapy.

12.
Heliyon ; 10(2): e24202, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38293469

RESUMEN

A series of new imidazole-phenazine derivatives were synthesized via a two-step process. The condensation of 2,3-diaminophenazine and benzaldehyde derivatives proceeds with intermediate formation of an aniline Schiff base, which undergoes subsequent cyclodehydrogenation in situ. The structures of the synthesized compounds were characterized by 1D and 2D NMR, FTIR and HRMS. A total of thirteen imidazole phenazine derivatives were synthesized and validated for their inhibitory activity as anti-dengue agents by an in vitro DENV2 NS2B-NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Two para-substituted imidazole phenazines, 3e and 3k, were found to be promising lead molecules for novel NS2B-NS3 protease inhibitors with IC50 of 54.8 µM and 71.9 µM, respectively, compared to quercetin as a control (IC50 104.8 µM). The in silico study was performed using AutoDock Vina to identify the binding energy and conformation of 3e and 3k with the active site of the DENV2 NS2B-NS3 protease Wichapong model. The results indicate better binding properties of 3e and 3k with calculated binding energies of -8.5 and -8.4 kcal mol-1, respectively, compared to the binding energy of quercetin of -7.2 kcal mol-1, which corroborates well with the experimental observations.

13.
RSC Adv ; 14(6): 4097-4104, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38292272

RESUMEN

Cancer is currently one of the biggest causes of death in the world. Like some microorganisms, cancer cells also develop resistance to various chemotherapy drugs and are termed multidrug resistant (MDR). In this regard, there is a need to develop new alternative anticancer agents. Anticancer peptides (ACPs) with high selectivity and high cell penetration ability are a promising candidate, as well as they are easy to modify. A cyclohexapeptide called nocardiotide A was isolated from the marine sponge Callyspongia sp., which is cytotoxic towards several cancer cells such as MM, 1S, HeLa, and CT26 cells. Previously, nocardiotide A was synthesized with a very low yield owing to its challenging cyclization process. In this study, we synthesized [d-Ala]-nocardiotide A as a derivative of nocardiotide A using a combination of solid phase peptide synthesis (SPPS) and liquid phase peptide synthesis (LPPS). The synthesis was carried out by selecting a d-alanine residue at the C-terminus to give a desired cyclic peptide product with a yield of 31% after purification. The purified [d-Ala]-nocardiotide A was characterized using HR-ToF MS and 1H and 13C-NMR spectroscopy to validate the desired product. The anticancer activity of the peptide was determined against HeLa cancer cell lines with an IC50 value of 52 µM compared to the parent nocardiotide A with an IC50 value of 59 µM. In the future, we aim to mutate various l-amino acids in nocardiotide A to d-amino acids to prepare nocardiotide A derivatives with a higher activity to kill cancer cells with higher membrane permeation. In addition, the mechanism of action of nocardiotide A and its derivatives will be evaluated.

14.
Fitoterapia ; 173: 105765, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38042506

RESUMEN

A phytochemical study on the bark of Chisocheton erythrocarpus Hiern (Meliaceae) has led to the isolation of six new phragmalin-type limonoids named erythrocarpines I - N (1-6) along with one known limonoid, erythrocarpine F (7). Their structures were fully characterized by spectroscopic methods. The pre-treatment of NG108-15 cells with 1-5, 7 (2 h) demonstrated low to good protective effects against H2O2 exposure; 1 (83.77% ± 1.84 at 12.5 µM), 2 (69.07 ± 2.01 at 12.5 µM), 3 (80.38 ± 2.1 at 12.5 µM), 4 (62.33 ± 1.95 at 25 µM),5 (58.67 ± 1.85 at 50 µM) and 7 (66.07 ± 2.03 at 12.5 µM). Interestingly, 1 and 3 demonstrated comparable protective effects to positive control epigallocatechin gallate (EGCG) with similar cell viability capacity (≈ 80%), having achieved that at lower concentration (12.5 µM) than EGCG (50 µM). Collectively, the results suggested the promising use of 1 and 3 as potential neuroprotective agents against hydrogen peroxide-induced cytotoxicity in neuronal model.


Asunto(s)
Limoninas , Meliaceae , Fármacos Neuroprotectores , Estructura Molecular , Fármacos Neuroprotectores/farmacología , Peróxido de Hidrógeno , Limoninas/farmacología , Limoninas/química , Meliaceae/química
15.
Molecules ; 28(23)2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-38067508

RESUMEN

Peptide compounds play a significant role in medicinal chemistry as they can inhibit the activity of species that cause malaria. This literature review summarizes the isolation of antimalarial peptides, the synthesis method with the detailed structure and sequences of each peptide, and discusses the biological activity of the isolated and synthesized compounds. The synthetic routes and reactions for cyclic and linear antimalarial peptides are systematically highlighted in this review including preparing building blocks, protection and deprotection, coupling and cyclization reactions until the target compound is obtained. Based on the literature data and the results, this review's aim is to provide information to discover and synthesize more antimalarial peptide for future research.


Asunto(s)
Antimaláricos , Malaria , Humanos , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Péptidos/química , Malaria/tratamiento farmacológico , Ciclización , Química Farmacéutica , Péptidos Cíclicos/uso terapéutico
16.
Toxins (Basel) ; 15(12)2023 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-38133190

RESUMEN

The genus Biscogniauxia, a member of the family Xylariaceae, is distributed worldwide with more than 50 recognized taxa. Biscogniauxia species is known as a plant pathogen, typically acting as a parasite on tree bark, although certain members of this genus also function as endophytic microorganisms. Biscogniauxia endophytic strain has received attention in many cases, which includes constituent research leading to the discovery of various bioactive secondary metabolites. Currently, there are a total of 115 chemical compounds belonging to the class of secondary metabolites, and among these compounds, fatty acids have been identified. In addition, the strong pharmacological agents of this genus are (3aS,4aR,8aS,9aR)-3a-hydroxy-8a-methyl-3,5-dimethylenedecahydronaphto [2,3-b]furan-2(3H)-one (HDFO) (antifungal), biscopyran (phytotoxic activity), reticulol (antioxidant), biscogniazaphilone A and B (antimycobacterial), and biscogniauxone (Enzyme GSK3 inhibitor). This comprehensive research contributes significantly to the potential discovery of novel drugs produced by Biscogniauxia and holds promise for future development. Importantly, it represents the first-ever review of natural products originating from the Biscogniauxia genus.


Asunto(s)
Hongos , Glucógeno Sintasa Quinasa 3 , Hongos/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Antifúngicos/farmacología , Plantas/metabolismo
17.
Asian Pac J Cancer Prev ; 24(12): 4155-4165, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38156851

RESUMEN

OBJECTIVE: Cervical cancer is a malignancy originating from the cervix and often caused by oncogenic Human Papilloma Virus (HPV), specifically subtypes 16 and 18. Anticancer drugs are chemotherapeutic compounds used for cancer treatment. Therefore, this research aims to synthesize and characterize Zinc (II) dichloroethylenediamine (Zn(en)Cl2) complex, as well as determine its antiproliferative activity against HeLa cells. The Zn(en)Cl2 complex was successfully synthesized, and the antiproliferative activity was tested. METHODS: The synthesis involved reacting ethylenediamine and KCl with Zn metal. The complex formed was characterized using a conductometer, UV-Vis spectroscopy, FT-IR spectroscopy, and XRD, while the activity was measured against HeLa cells. RESULT: The synthesis yielded a 56.12% conversion with a melting point of 198-200 oC and a conductivity value of 2.02 mS/cm. The Zn(en)Cl2 complex showed potential activity against HeLa cells with an IC50 value of 898.35 µg/mL, which was evidenced by changes in the morphological structure of HeLa cells. Its interaction with DNA targets was investigated by employing molecular docking. CONCLUSION: The observed data indicated that the Zn(en)Cl2 complex bound to DNA at the nitrogenous base Guanine (DG) by coordinate covalent bonds. Interestingly, DG maintained interaction with the complex until the end of the docking simulation. Additionally, molecular dynamics (MD) simulation was conducted, and the results showed that Zn(en)Cl2 remained bound to the DNA binding pocket all through the process.


Asunto(s)
Antineoplásicos , Neoplasias del Cuello Uterino , Humanos , Femenino , Zinc/farmacología , Células HeLa , Simulación del Acoplamiento Molecular , Neoplasias del Cuello Uterino/tratamiento farmacológico , Cuello del Útero/metabolismo , Espectroscopía Infrarroja por Transformada de Fourier , Antineoplásicos/química , ADN , Ligandos
18.
Mol Divers ; 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37884781

RESUMEN

Cisplatin is a cancer medication widely used today, but it still poses some problems due to its toxic properties in the body. To overcome this issue, a new complex has been developed as a potential anticancer drug prospect by minimizing its toxic consequences. A novel Zn(II)IleDTC complex containing isoleucine dithiocarbamate ligands has been produced and analyzed using a range of analytical and spectroscopic methods. The Zn(II) IleDTC complex were characterized using various methods, including UV-Vis spectroscopy, FT-IR, determination of melting point, conductivity, and HOMO-LUMO analysis. Furthermore, computational NMR spectrum analysis was conducted in this study. Molecular docking studies was conducted to evaluate the potential of Zn(II) isoleucine dithiocarbamate as an HIF1 inhibitor. The results showed that the Zn complex exhibited a good docking score of -6.6 and formed hydrogen bonds with ARG 17, VAL264, and GLU15, alkyl bonds with TRP27 and LEU32, and Pi-Alkyl bonds with PRO41 and ARG44. This suggests that the Zn(II) isoleucine dithiocarbamate complex could be a promising candidate for cancer treatment with potential HIF1 inhibition properties. To assess the dynamic stability and efficacy of protein-ligand interactions over time, molecular dynamics simulations was conducted for both individual proteins and protein complexes. The cytotoxicity evaluation of Zn(II) isoleucine dithiocarbamate against MCF-7 cells obtained an IC50 value of 362.70 µg/mL indicating moderate cytotoxicity and morphological changes of cancer cells causing cancer cells to undergo apoptosis. The Zn(II) isoleucine dithiocarbamate complex may have promising potential as an anticancer compound due to its significant inhibitory effect on the breast cancer cell line (MCF7). According to the ADMET study, the complex exhibits drug-like characteristics with low toxicity, further supporting its potential as a viable drug candidate.

19.
Heliyon ; 9(10): e20710, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37860547

RESUMEN

We synthesised and biologically evaluated two new hybrid probes [131I]BPF-01 and [131I]BPF-02 which were built from three structural entities: benzothiazole-phenyl, fluorescein isothiocyanate (FITC), and iodine-131. These probes were designed for potential applications in assisting surgical procedures of solid cancers. The cytotoxicity study demonstrated that fluorescent probes BPF-01 (31.23 µg/mL) and BPF-02 (250 µg/mL) were relatively not toxic to normal immortalized human keratinocytes (HaCaT) cells, as indicated by the percentage of cell survival above 50 %. Furthermore, both probes displayed low to moderate anticancer activity against the breast cancer cells (MDA-MB-231) and prostate cancer cells (LNCaP and DU-145). The probe BPF-01 apparently showed an accumulation in the tumour tissues, as suggested by ex vivo fluorescence examinations. In addition, the cellular uptake study suggests that hybrid probe [131I]-BPF-01 was potentially accumulated in the MCF-7 cell line with the highest uptake of 16.11 ± 1.52 % after 2 h of incubation, approximately 50-fold higher than the accumulation of iodine-131 (control). The magnetic bead assay suggests that [131I]-BPF-02 and [131I]-BPF-02 showed a promising capability to interact with translocator protein 18 kDa (TSPO). Moreover, the computational data showed that the binding scores for ligands 7-8, BPF-01 and BPF-02, and [131I]-BPF-01 and [131I]-BPF-02 in the TSPO were considerably high. Accordingly, fluorescent probes BPF-01 and BPF-02, and hybrid probes [131I]BPF-01 and [131I]BPF-02 can be further developed for targeting cancer cells during intraoperative tumour surgery.

20.
Molecules ; 28(15)2023 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-37570872

RESUMEN

Murraya is a plant genus within the Rutaceae family comprising over 17 species, which are widely distributed in Asia, Australia, and the Pacific Islands. Furthermore, these species have been used in traditional medicine to treat fever, pain, and dysentery. Several reports have also extensively studied the leaves, seeds, stembark, and bark of Murraya from 1965 to 2023 to explore their natural product composition. Various phytochemical studies have revealed the isolation of 413 compounds recorded, comprising coumarins, terpenoids, flavonoids, and aromatics, as well as alkaloids, which constitute the largest proportion (46.9%). These isolated compounds have long been known to exhibit different bioactivities, such as cytotoxic and anti-inflammatory properties. Cytotoxic activity has been observed against HCT 116, HeLa, HepG2, and other cell lines. Previous studies have also reported the presence of antifungal, hepatoprotective, antihyperlipidemic, antidiarrheal, and antioxidant effects. Therefore, this review provides a comprehensive overview of Murraya species, highlighting their phytochemistry, biological activities, and potential as a source of active natural compounds.


Asunto(s)
Alcaloides , Murraya , Rutaceae , Medicina Tradicional , Extractos Vegetales/farmacología , Extractos Vegetales/química , Fitoquímicos/farmacología , Fitoquímicos/química , Etnofarmacología , Fitoterapia
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