RESUMO
Fatalities caused by infectious diseases (i.e., diseases caused by parasite, bacteria, and viruses) have become reinstated as a major public health threat globally. Factors such as antimicrobial resistance and viral complications are the key contributors to the death numbers. As a result, new compounds with structural diversity classes are critical for controlling the virulence of pathogens that are multi-drug resistant. Derivatization of bio-active organic molecules with organometallic synthons is a promising strategy for modifying the inherent and enhanced properties of biomolecules. Due to their redox chemistry, bioactivity, and structural diversity, organometallic moieties make excellent candidates for lead structures in drug development. Furthermore, organometallic compounds open an array of potential in therapy that existing organic molecules lack, i.e., their ability to fulfill drug availability and resolve the frequent succumbing of organic molecules to drug resistance. Additionally, metal complexes have the potential towards metal-specific modes of action, preventing bacteria from developing resistance mechanisms. This review's main contribution is to provide a thorough account of the biological efficacy (in vitro and in vitro) of metal-based complexes against infectious diseases. This resource can also be utilized in conjunction with corresponding journals on metal-based complexes investigated against infectious diseases.
Assuntos
Doenças Transmissíveis , Complexos de Coordenação , Humanos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Virulência , Desenvolvimento de Medicamentos , Saúde PúblicaRESUMO
Fifteen rhenium(I) tricarbonyl complexes of the form fac-[Re(N,O')(CO)3(X)], where N,O'-bidentate ligand = 2-picolinic acid (Pico); 3,5-difluoropyridine-2-carboxylic acid (Dfpc); 3-trifluoromethyl-pyridine-2-carboxylic acid (Tfpc) and X = H2O; pyrazole (Pz); pyridine (Py); imidazole (Im); and methanol (CH3OH) were synthesized using the '2 + 1' mixed ligand approach with an average yield of 84%. The complexes were characterized using the following spectroscopic techniques: IR, 1H and 13C NMR, UV/Vis, and single-crystal X-ray diffraction. The effect of the fluorine atoms on the backbone of the N,O'-bidentate ligand was investigated and a trend was noticed in the carbonyl stretching frequencies: with Pico < Tfpc < Dfpc. The in vitro biological screening on Vero (healthy mammalian), HeLa (cervical carcinoma) and A549 (lung cancer) cells revealed one toxic complex, fac-[Re(Pico)(CO)3(H2O)], with respective LC50 values of 9.0 ± 0.9, 15.8 ± 4.9 (SI = 0.570) and 20.9 ± 0.8 (SI = 0.430) µg/mL. As a result, it can be used as a positive control drug of toxicity.
Assuntos
Neoplasias Pulmonares , Rênio , Animais , Humanos , Modelos Moleculares , Ligantes , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Rênio/química , Estrutura Molecular , MamíferosRESUMO
Globally, cancer is the second (to cardiovascular diseases) leading cause of death. Regardless of various efforts (i.e., finance, research, and workforce) to advance novel cancer theranostics (diagnosis and therapy), there have been few successful attempts towards ongoing clinical treatment options as a result of the complications posed by cancerous tumors. In recent years, the application of magnetic nanomedicine as theranostic devices has garnered enormous attention in cancer treatment research. Magnetic nanoparticles (MNPs) are capable of tuning the magnetic field in their environment, which positively impacts theranostic applications in nanomedicine significantly. MNPs are utilized as contrasting agents for cancer diagnosis, molecular imaging, hyperfusion region visualization, and T cell-based radiotherapy because of their interesting features of small size, high reactive surface area, target ability to cells, and functionalization capability. Radiolabelling of NPs is a powerful diagnostic approach in nuclear medicine imaging and therapy. The use of luminescent radioactive rhenium(I), 188/186Re, tricarbonyl complexes functionalised with magnetite Fe3O4 NPs in nanomedicine has improved the diagnosis and therapy of cancer tumors. This is because the combination of Re(I) with MNPs can improve low distribution and cell penetration into deeper tissues.
Assuntos
Nanopartículas de Magnetita/química , Neoplasias/diagnóstico , Rênio/química , Nanomedicina Teranóstica/métodos , Animais , Humanos , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Compostos Organometálicos/químicaRESUMO
Species within the genus Rhoicissus (Vitaceae) are commonly used in South African traditional medicine. The current review discusses the occurrence, distribution, traditional uses, phytochemistry, and pharmacological properties of Rhoicissus species covering the period 1981-2020. The data reported were systematically collected, read, and analysed from scientific electronic databases including Scopus, Scifinder, Pubmed, and Google Scholar. Reported evidence indicates that species in this genus are used for the treatment of gastrointestinal complaints, sexually transmitted infections (STIs), and infertility, as well as to tone the uterus during pregnancy and to facilitate delivery. Pharmacological studies have further shown that members of the Rhoicissus genus display antidiabetic, uterotonic, ascaricidal, hepatoprotective, antioxidant, antimicrobial, anticancer, and anti-inflammatory properties. They are linked to the presence of bioactive compounds isolated from the genus. Hence, Rhoicissus species can potentially be an alternative therapeutic strategy to treat diseases and develop safer and more potent drugs to combat diseases. Plant species of this genus have valuable medicinal benefits due to their significant pharmacological potential. However, scientific investigation and information of the therapeutic potential of Rhoicissus remain limited as most of the species in the genus have not been fully exploited. Therefore, there is a need for further investigations to exploit the therapeutic potential of the genus Rhoicissus. Future studies should evaluate the phytochemical, pharmacological, and toxicological activities, as well as the mode of action, of Rhoicissus crude extracts and secondary compounds isolated from the species.
Assuntos
Compostos Fitoquímicos/química , Vitaceae/química , Vitaceae/metabolismo , Animais , Antioxidantes/química , Humanos , Medicina Tradicional/métodos , Extratos Vegetais/químicaRESUMO
Carissa, a genus of the Apocynaceae family, consists of evergreen species, such as shrubs as well as small trees that are native to Asia, Africa, and Oceania's subtropical and tropical regions. Most of the Carissa species are traditionally used to treat various diseases, such as chest pain, headaches, gonorrhoea, rheumatism, syphilis, oedema, rabies, stomach pain, hepatitis, cardiac diseases, and asthma. The pharmacological studies on Carissa species revealed its antioxidant, antimicrobial, anticancer, cardioprotective, antipyretic, analgesic, wound healing, anticonvulsant, antiarthritic, adaptogenic, anti-inflammatory, and antidiabetic activities, thus validating its use in indigenous medicine systems. The review article summarised the comprehensive literature available, including morphology, indigenous uses, bioactive composition, nutraceutical, and pharmacological activities of Carissa species. A total of 155 research papers were cited in this review article. The Carissa fruits are rich in dietary fibre, lipids, proteins, carbohydrates, vitamin C, and macro- and micro-elements. A total of 121 compounds (35 polyphenols (flavonoids and phenolic acids), 30 lignans, 41 terpenoids, 7 steroids, 2 coumarins, and 6 cardiac glycosides) have been extracted from C. spinarum, C. carandas, and C. macrocarpa. Among all chemical constituents, lupeol, carissol, naringin, carisssone, scopoletin, carissaeduloside A, D, J, carandinol, sarhamnoloside, carissanol, olivil, carinol, 3ß-hydroxyolean-11-en-28,13ß-oilde, ursolic acid, and carissone are the key bioactive constituents responsible for pharmacological activities of genus Carissa. The gathered ethnopharmacological information in the review will help to understand the therapeutic relevance of Carissa as well as paving a way for further exploration in the discovery of novel plant-based drugs.
Assuntos
Apocynaceae/química , Suplementos Nutricionais , Etnofarmacologia , Compostos Fitoquímicos , Plantas Medicinais/química , África , Animais , Ásia , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêuticoRESUMO
BACKGROUND: Prostate Cancer (PCa) is the second most diagnosed urological cancer among men worldwide. Conventional methods used for diagnosis of PCa have several pitfalls which include lack of sensitivity and specificity. On the other hand, traditional treatment of PCa poses challenges such as long-term side effects and the development of multidrug resistance (MDR). MAIN BODY: Hence, there is a need for novel PCa agents with the potential to lessen the burden of these adverse effects on patients. Nanotechnology has emerged as a promising approach to support both early diagnosis and effective treatment of tumours by ensuring precise delivery of the drug to the targeted site of the disease. Most cancer-related biological processes occur on the nanoscale hence application of nanotechnology has been greatly appreciated and implemented in the management and therapeutics of cancer. Nuclear medicine plays a significant role in the non-invasive diagnosis and treatment of PCa using appropriate radiopharmaceuticals. This review aims to explore the different radiolabelled nanomaterials to enhance the specific delivery of imaging and therapeutic agents to cancer cells. Thereafter, the review appraises the advantages and disadvantages of these modalities and then discusses and outlines the benefits of radiolabelled nanomaterials in targeting cancerous prostatic tumours. Moreover, the nanoradiotheranostic approaches currently developed for PCa are discussed and finally the prospects of combining radiopharmaceuticals with nanotechnology in improving PCa outcomes will be highlighted. CONCLUSION: Nanomaterials have great potential, but safety and biocompatibility issues remain. Notwithstanding, the combination of nanomaterials with radiotherapeutics may improve patient outcomes and quality of life.
RESUMO
Dehydroandrographolide (DA) was isolated and experimentally characterized utilizing FT-IR, UV-Vis, and NMR spectroscopy techniques along with detailed theoretical modelled at the DFT/B3LYP-D3BJ/6-311 + + G(d,p) level of theory. Substantially, molecular electronic property investigations in the gaseous phase alongside five different solvents (ethanol, methanol, water, acetonitrile and DMSO) were comprehensively reported and compared with the experimental results. The globally harmonized scale (GHS), which is used to identify and label chemicals, was also utilized to demonstrate that the lead compound predicted an LD50 of 1190 mg/kg. This finding implies that consumers can safely consume the lead molecule. Notable impacts on hepatotoxicity, cytotoxicity, mutagenicity, and carcinogenicity were likewise found to be minimal to nonexistent for the compound. Additionally, in order to account for the biological performance of the studied compound, in-silico molecular docking simulation analysis was examined against different anti-inflammatory target of enzymes (3PGH, 4COX, and 6COX). From the examination, it can be inferred that DA@3PGH, DA@4COX, and DA@6COX, respectively, showed significant negative binding affinities of -7.2 kcal/mol, -8.0 kcal/mol, and - 6.9 kcal/mol. Thus, the high mean binding affinity in contrast to conventional drugs further reinforces these results as an anti-inflammatory agent.
Assuntos
Anti-Inflamatórios , Diterpenos , Análise Espectral Raman , Simulação de Acoplamento Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Espectroscopia de Ressonância Magnética , Anti-Inflamatórios/farmacologia , Espectrofotometria UltravioletaRESUMO
The crystal structure of the racemic title compound, C20H16Cl2N4 is described, where the formation of a di-substituted 6,8-di-chloro quinoxaline, containing two stereogenic centres, is confirmed.
RESUMO
In view of the research-substantiated comparative efficiency of nontoxic and bioavailable nanomaterials synergic with human systems for drug delivery, this work was aimed at studying the comparative efficiency of transition metal (Au, Os, and Pt)-decorated B12N12 nanocages in the adsorption of fluorouracil (5Fu), an antimetabolite-classed anticarcinogen administered for cancers of the breast, colon, rectum, and cervix. Three different metal-decorated nanocages interacted with 5Fu drug at the oxygen (O) and fluorine (F) sites, resulting in six adsorbent-adsorbate systems whose reactivity and sensitivity were investigated using density functional theory computation at the B3LYP/def2TZVP level of theory with special emphasis on the structural geometry, electronic, and topology analysis as well as the thermodynamic properties of the systems. While the electronic studies predicted Os@F as having the lowest and most favorable Egp and Ead of 1.3306 eV and -11.9 kcal/mol, respectively, the thermodynamic evaluation showed Pt@F to have the most favorable thermal energy (E), heat capacity (Cp), and entropy (ΔS) values as well as negative ΔH and ΔG while the adsorption studies showed that the greatest degree of chemisorption with Ead magnitude of -204.5023 kcal/mol was observed in energies ranging from -12.0 to 138.4 kcal/mol with Os@F and Au@F at the lower and upper borders. The quantum theory of atoms in molecules results show that the six systems had noncovalent interactions as well as a certain degree of partial covalency but none showed covalent interaction while the noncovalent interaction analysis corroborated this by showing that the six systems had favorable interactions, though of varying degrees, with very little trace of steric hindrance or electrostatic interactions. Overall, the study showed that notwithstanding the good performance of the six adsorbent systems considered, the Pt@F and Os@F showed the most favorable potential for the delivery of 5Fu.
Assuntos
Fluoruracila , Nanoestruturas , Humanos , Fluoruracila/uso terapêutico , Termodinâmica , Nanoestruturas/uso terapêutico , Adsorção , Sistemas de Liberação de MedicamentosRESUMO
Similar to the more well-known carbon nanotubes, gallium nitride nanotubes (GaNNT) are among the materials that scientists have found to be extremely helpful in transporting drugs and to provide significant potential for multi-modal medical therapies. Here, the potential of Cu, Ag, and Au-doped GaNNT for smart delivery of the anticancer medication hydroxyurea (HU) was extensively investigated employing quantum chemical analysis and density functional theory (DFT) computation at the B3LYP-GD3BJ/def2-SVP level of theory. The systematic approach used in this study entails examining the exo (outside)-and endo (inside) loading of HU utilizing the investigated nanotubes in order to understand the adsorption, sensing processes, bonding types, and thermodynamic properties. Results of the HOMO-LUMO studies show that metal-doped GaNNTs with the hydroxyurea (HU) at the endo - interaction of the drug of the nanotube produced more reduced energy gaps (0.911-2.039 eV) compared with metal-doped GaNNTs complexes at the outside - interaction of the drug on the nanotube (2.25-3.22 eV) and as such reveal their suitability for use as drug delivery materials. As observed in the endo-interaction of HU adsorptions in the tubes, HU_endo_Au@GaNNT possessed the highest adsorption energy values of -118.716 kcal/mol which shows the most chemisorption between the surfaces and the adsorbate while for HU_exo_Ag@GaNNT is -97.431 kcal/mol for the highest exo-interactions. These results suggest that HU drug interacted inside the Ag, Au, and Cu doped GaNNT will be very proficient as a carrier of the HU drug into bio systems. These results are along with visual studies of weak interactions, thermodynamics, sensor, and drug release mechanisms suggest strongly the endo-encapsulation of HU as the best mode for smart drug delivery.
Assuntos
Antineoplásicos , Gálio , Nanotubos de Carbono , Hidroxiureia , Nanotubos de Carbono/química , Gálio/químicaRESUMO
Theoretical examination of hydroxyurea adsorption capabilities toward the cyclodextrin surface for proper drug delivery systems was carried out utilizing DFT simulations. The study aims to assess the efficacy of doped cyclodextrin (doped with boron, nitrogen, phosphorus, and sulfur atoms) in increasing its stability and efficiency in intermolecular interactions, hence facilitating optimal drug delivery. The adsorption energies were found to follow a decreasing order of B@ACD-HU>N@ACD-HU>P@ACD-HU>S@ACD-HU with energies of -0.046, -0.0326, -0.015, and 0.944 kcal/mol, respectively. The S@ACD-HU complex, unlike previous systems, had a physical adsorption energy. The N@ACD-HU and B@ACD-HU complexes had the shortest bond lengths of 1.42 Å (N122-C15) and 1.54 Å (B126-C15), respectively. The HOMO and LUMO values were also high in identical systems, -6.367 and -2.918 eV (B@ACD-HU) and -6.278 and -1.736 eV (N@ACD-HU), respectively, confirming no chemical interaction. The N@ACD-HU has the largest energy gap of 4.54 eV. For the QTAIM analysis and plots, the maximum electron density and ellipticity index were detected in B@ACD-HU, 0.600 au (H70-N129) and 0.8685 au (H70-N129), respectively, but N@ACD-HU exhibited a high Laplacian energy of 0.7524 a.u (H133-N122). The fragments' TDOS, OPDOS, and PDOS exhibited a strong bond interaction of greater than 1, and they had different Fermi levels, with the highest value of -8.16 eV in the N@ACD-HU complex. Finally, the NCI analysis revealed that the complexes were noncovalent. According to the literature, the van der Waals form of interactions is used in the intermolecular forces of cyclodextrin cavities. The B@ACD-HU and N@ACD-HU systems were more greenish in color with no spatial interaction. These two systems have outperformed other complexes in intermolecular interactions, resulting in more efficient drug delivery. They had the highest negative adsorption energies, the shortest bond length, the highest HOMO/LUMO energies, the highest energy gap, the highest stabilization energy, the strongest bonding effect, the highest electron density, the highest ellipticity index, and a strong van der Waals interaction that binds the drug and the surface together.
RESUMO
Rhenium complexes have been observed experimentally to exhibit good inhibitory activity against malignant cells. Hence, our motivation is to explore this activity from a theoretical perspective. In the present study, density functional theory (DFT) and in silico molecular docking approaches were utilized to unravel the unique properties of metal-based rhenium tricarbonyl complexes as effective anticancer drugs. All DFT calculations and geometric optimizations were conducted using the well-established hybrid functional B3LYP-GD(BJ)/Gen/6-311++G(d,p)/LanL2DZ computational method. The FT-IR spectroscopic characterization of the complexes: fac-[Re(Pico)(CO)3(Pz)] (R1), fac-[Re(Pico)(CO)3(Py)] (R2), fac-[Re(Dfpc)(CO)3(H2O)] (R3), fac-[Re(Dfpc)(CO)3(Pz)] (R4), fac-[Re(Dfpc)(CO)3(Py)] (R5), fac-[Re(Tfpc)(CO)3(H2O)] (R6), fac-[Re(Tfpc)(CO)3(Py)] (R7), and fac-[Re(Tfpc)(CO)3(Im)] (R8) was explored. To gain insights into the electronic structural properties, bioactivity, and stability of these complexes, the highest occupied molecular orbital-lowest unoccupied molecular orbital analysis, binding energy, and topological analysis based on quantum theory of atoms-in-molecules were considered. The anticancer activities of the complexes were measured via in silico molecular docking against human BCL-2 protein (IG5M) and proapoptotic (agonist) BAX 1 protein (450O). The results showed that the studied complexes exhibited good binding affinity (-3.25 to -10.16 kcal/mol) and could cause significant disruption of the normal physiological functions of the studied proteins. The results of DFT calculations also showed that the studied complexes exhibited good stability and are suitable candidates for the development of anticancer agents.
RESUMO
Nanoparticles and nanotechnology developments continue to advance the livelihood of humankind. However, health challenges due to microorganisms and cancerous cells continue to threaten many people's lives globally. Therefore, new technological interventions are of great importance. The phytochemicals present in medicinal plants are suggested as biocompatible, cost-effective, and regenerative sources that can be utilized for the green synthesis of nanoparticles. Different plant extracts with various phytochemical constituents can form nanoparticles with specific shapes, sizes, and optical properties. This review focuses on advances in green nanotechnology and provides details on reliable synthetic routes toward medically and biocompatible relevant metallic nanoparticles. We cover a wide range of applications that use phytonanoparticles with an in-depth look at what makes these materials interesting. The study also provides details of the literature on the interventions made in phytonanotechnology for the production of plant-mediated synthesis and capped metallic nanoparticles and their applications in various industries. It was observed that a variety of plants have been well studied, and detailed findings have been reported; however, the study of Phyllanthus is still in its early stages, and more needs to be uncovered.
RESUMO
In this study, two novel derivatives of naphthalene-2-sulfonic acid: 6-(((1S,5R)-3,5-dichloro-2,4,6-triazabicyclo [z3.1.0]hex-3-en-1-yl)amino)-5-((E)-phenyldiazenyl)naphthalene-2-sulfonic acid (DTPS1) and (E)-6-((4,6-dichloro-1,3,5-triazine2-yl)amino)-4-hydroxy-3-(phenyldiazenyl)naphthalene-2-sulfonic acid (DTPS2) have been synthesized and characterized using FT-IR, UV-vis, and NMR spectroscopic techniques. Applying density functional theory (DFT) at the B3LYP, APFD, PBEPBE, HCTH, TPSSTPSS, and ωB97XD/aug-cc-pVDZ level of theories for the electronic structural properties. In-vitro analysis, molecular docking, molecular dynamic (MD) simulation of the compounds was conducted to investigate the anti-inflammatory potential using COXs enzymes. Docking indicates binding affinity of -9.57, -9.60, -6.77 and -7.37 kcal/mol for DTPS1, DTPS2, Ibuprofen and Diclofenac which agrees with in-vitro assay. Results of MD simulation, indicates sulphonic group in DTPS1 has > 30% interaction with the hydroxyl and oxygen atoms in amino acid residues, but > 35% interaction with the DTPS2. It can be said that the DTPS1 and DTPS2 can induce inhibitory effect on COXs to halt biosynthesis of prostaglandins (PGs), a chief mediator of inflammation and pain in mammals.Communicated by Ramaswamy H. Sarma.
Assuntos
Anti-Inflamatórios , Simulação de Dinâmica Molecular , Animais , Simulação de Acoplamento Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Anti-Inflamatórios/farmacologia , Percepção , MamíferosRESUMO
Theoretical studies on the adsorption, sensibility, and reactivity of a boron nitride nanocage decorated with Au, Cu, Ni, Os, Pt, and Zn metals as a biosensor material were carried out for the adsorption of carboplatin by applying the density functional theory computation at the B3LYP-GD3BJ/def2svp level of theory. All the optimized structures, as well as the calculations as regards the studied objective including electronic properties, geometry optimization parameters, adsorption energy studies, natural bond orbital analysis, topology studies, sensor mechanistic parameters, and thermodynamic properties (ΔG and ΔH), were investigated herein. As a result, the noticeable change in the energy gap of the studied surfaces when interacting with carboplatin accounted for the surfaces' reactivity, stability, conductivity, work function, and overall adsorption ability, implying that the studied decorated surfaces are good sensor materials for sensing carboplatin. Furthermore, the negative adsorption energies obtained for interacting surfaces decorated with Cu, Ni, Os, and Zn suggest that the surface has a superior ability to sense carboplatin as chemisorption was seen. Substantially, the geometric short adsorption bond length after adsorption, thermodynamically spontaneous reactions, and acceptable sensor mechanism results demonstrate that the investigated surfaces have strong sensing characteristics for sensing carboplatin.
RESUMO
Chronic wounds are ubiquitously inhabited by bacteria, and they remain a challenge as they cause significant discomfort and because their treatment consumes huge clinical resources. To reduce the burden that chronic wounds place upon both patients and health services, a wide variety of approaches have been devised and investigated. Bioinspired nanomaterials have shown great success in wound healing when compared to existing approaches, showing better ability to mimic natural extracellular matrix (ECM) components and thus to promote cell adhesion, proliferation, and differentiation. Wound dressings that are based on bioinspired nanomaterials can be engineered to promote anti-inflammatory mechanisms and to inhibit the formation of microbial biofilms. We consider the extensive potential of bioinspired nanomaterials in wound healing, revealing a scope beyond that covered previously.
Assuntos
Anti-Infecciosos , Nanoestruturas , Humanos , Cicatrização , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêuticoRESUMO
BACKGROUND: Stigmasterol is an unsaturated phytosterol that belong to the class of tetracyclic steroids abundant in Rhoicissus tridentata. Stigmasterol is an important constituent since it has shown impressive pharmacological effects such as anti-osteoarthritis, anticancer, anti-diabetic, anti-inflammatory, antiparasitic, immunomodulatory, antifungal, antioxidant, antibacterial, and neuroprotective activities. Furthermore, due to the presence of π system and hydroxyl group, stigmasterol is readily derivatized through substitution and addition reactions, allowing for the synthesis of a wide variety of stigmasterol derivatives. METHODS: Stigmasterol (1) isolated from Rhoicissus tridentata was used as starting material to yield eight bio-active derivatives (2-9) through acetylation, epoxidation, epoxide ring opening, oxidation, and dihydroxylation reactions. The structures of all the compounds were established using spectroscopic techniques, NMR, IR, MS, and melting points. The synthesized stigmasterol derivatives were screened for cytotoxicity against the hormone receptor-positive breast cancer (MCF-7), triple-negative breast cancer (HCC70), and non-tumorigenic mammary epithelial (MCF-12 A) cell lines using the resazurin assay. RESULTS: Eight stigmasterol derivatives were successfully synthesized namely; Stigmasterol acetate (2), Stigmasta-5,22-dien-3,7-dione (3), 5,6-Epoxystigmast-22-en-3ß-ol (4), 5,6-Epoxystigmasta-3ß,22,23-triol (5), Stigmastane-3ß,5,6,22,23-pentol (6), Stigmasta-5-en-3,7-dion-22,23-diol (7), Stigmasta-3,7-dion-5,6,22,23-ol (8) and Stigmast-5-ene-3ß,22,23-triol (9). This is the first report of Stigmasta-5-en-3,7-dion-22,23-diol (7) and Stigmasta-3,7-dion-5,6,22,23-ol (8). The synthesized stigmasterol analogues showed improved cytotoxic activity overall compared to the stigmasterol (1), which was not toxic to the three cell lines tested (EC50 Ë 250 µM). In particular, 5,6-Epoxystigmast-22-en-3ß-ol (4) and stigmast-5-ene-3ß,22,23-triol (9) displayed improved cytotoxicity and selectivity against MCF-7 breast cancer cells (EC50 values of 21.92 and 22.94 µM, respectively), while stigmastane-3ß,5,6,22,23-pentol (6) showed improved cytotoxic activity against the HCC70 cell line (EC50: 16.82 µM). CONCLUSION: Natural products from Rhoicissus tridentata and their derivatives exhibit a wide range of pharmacological activities, including anticancer activity. The results obtained from this study indicate that molecular modification of stigmasterol functional groups can generate structural analogues with improved anticancer activity. Stigmasterol derivatives have potential as candidates for novel anticancer drugs.
Assuntos
Antineoplásicos , Neoplasias , Estigmasterol/farmacologia , Propilenoglicóis , Antineoplásicos/farmacologia , AntibacterianosRESUMO
Nanostructures such as nanosheets, nanotubes, nanocages, and fullerenes have been extensively studied as potential candidates in various fields since the advancement of nanoscience. Herein, the interaction between biguanides (BGN) and metformin (MET) on the modified covalent organic framework (COF), COF-B, and COF-Al was investigated using density functional theory at the ωB97XD/6-311+G (d, p) level of computation to explore a new drug delivery system. The electronic properties evaluation reveals that the studied surfaces are suited for the delivery of both drug molecules. The calculated adsorption energies and basis set superposition errors (BSSE) ranged between -21.20 and -65.86 kJ/mol. The negative values obtained are an indication of excellent interaction between the drug molecules and the COF surfaces. Moreover, BGN is better adsorbed on COF-B with Eads of -65.86 kJ/mol, while MET is better adsorbed on COF-Al with Eads = -47.30 kJ/mol. The analysis of the quantum theory of atom in molecules (QTAIM) explained the nature and strength of intermolecular interaction existing between the drug molecules BGN and MET with the adsorbing surfaces. The analysis of noncovalent interaction (NCI) shows a weak hydrogen-bond interaction. Other properties such as quantum chemical descriptors and natural bond orbital (NBO) analysis also agree with the potential of COF surfaces as drug delivery systems. The electron localization function (ELF) is discussed, and it confirms the transitions occurring in the NBO analysis of the complexes. In conclusion, COF-B and COF-Al are suitable candidates for the effective delivery of BGN and MET.
Assuntos
Estruturas Metalorgânicas , Metformina , Estruturas Metalorgânicas/química , Preparações Farmacêuticas , Porosidade , Ligação de HidrogênioRESUMO
In the original publication [...].
RESUMO
Rubus ellipticus fruits aqueous extract derived ZnO-nanoparticles (NPs) were synthesized through a green synthesis method. The structural, optical, and morphological properties of ZnO-NPs were investigated using XRD, FTIR, UV-vis spectrophotometer, XPS, FESEM, and TEM. The Rietveld refinement confirmed the phase purity of ZnO-NPs with hexagonal wurtzite crystalline structure and p-63-mc space group with an average crystallite size of 20 nm. XPS revealed the presence of an oxygen chemisorbed species on the surface of ZnO-NPs. In addition, the nanoparticles exhibited significant in vitro antioxidant activity due to the attachment of the hydroxyl group of the phenols on the surface of the nanoparticles. Among all microbial strains, nanoparticles' maximum antibacterial and antifungal activity in terms of MIC was observed against Bacillus subtilis (31.2 µg/mL) and Rosellinia necatrix (15.62 µg/mL), respectively. The anticancer activity revealed 52.41% of A549 cells death (IC50: 158.1 ± 1.14 µg/mL) at 200 µg/mL concentration of nanoparticles, whereas photocatalytic activity showed about 17.5% degradation of the methylene blue within 60 min, with a final dye degradation efficiency of 72.7%. All these results suggest the medicinal potential of the synthesized ZnO-NPs and therefore can be recommended for use in wastewater treatment and medicinal purposes by pharmacological industries.