QSAR prediction, synthesis, anticancer evaluation, and mechanistic investigations of novel sophoridine derivatives as topoisomerase I inhibitors.

Sophoridine, which is derived from the Leguminous plant Sophora alopecuroides L., has certain pharmacological activity as a new anticancer drug. Herein, a series of novel N-substituted sophoridine derivatives was designed, synthesized and evaluated with anticancer activity. Through QSAR prediction models, it was discovered that the introduction of a benzene ring as a main pharmacophore and reintroduced into a benzene in para position on the phenyl ring in the novel sophoridine derivatives improved the anticancer activity effectively. In vitro, 28 novel compounds were evaluated for anticancer activity against four human tumor cell lines (A549, CNE-2, HepG-2, and HEC-1-B). In particular, Compound 26 exhibited remarkable inhibitory effects, with an IC50 value of 15.6 µM against HepG-2 cells, surpassing cis-Dichlorodiamineplatinum (II). Molecular docking studies verified that the derivatives exhibit stronger binding affinity with DNA topoisomerase I compared to sophoridine. In addition, 26 demonstrated significant inhibition of DNA Topoisomerase I and could arrest cells in G0/G1 phase. This study provides valuable insights into the design and synthesis of N-substituted sophoridine derivatives with anticancer activity.

Evaluation of Microwave-Assisted Extraction Method for Preparation and Assessment of Thai Herbal Medicine Oral Tablets With Enriched Phytochemical Compounds.

In developing countries, populations have employed herbal medicines for primary health care because they are believed to be more appropriate to the human body and have less side effects than chemically synthesized drugs. The present study aimed to develop and evaluate herbal tablets incorporated with a Thai traditional medicinal extract, U-pa-ri-waat (URW), using microwave-assisted extraction (MAE). The extraction efficiency for URW using MAE and traditional solvent extraction was compared based on the percent yield after spray drying. URW tablets were prepared using the dry granulation method. The optimized products were assessed using standard characterization methods based on the United States and British Pharmacopeias. DPPH and ABTS radical scavenging assays were performed to analyze the antioxidant capacity of the microwave-assisted extracts. The results revealed that the flowability of the dry granule with added maltodextrin was improved compared to a granule without additives, as indicated by an angle of repose of 33.69 ± 2.0°, a compressibility index of 15.38 ± 0.66, and a Hausner's ratio of 1.18 ± 0.06. The resulting formulation produced flat tablets with uniform weight variation, hardness, thickness, friability, and optimum disintegration time. The URW extracts showed antioxidant activity and MAE with maltodextrin carrier displayed the strongest DPPH and ABTS radical activities with IC50 values of 1.60 ± 0.02 µg/mL and 4.02 ± 0.24 µg/mL, respectively. The URW tablet formulation passed the quality control tests. Storage of the formulation tablets for 90 days under accelerated conditions had minimal effects on tablet characteristics.

Synthesis and biological evaluation of quercetin and resveratrol peptidyl derivatives as potential anticancer and antioxidant agents.

Quercetin and resveratrol are polyphenolic compounds, members of the flavonoid and the stilbene family, respectively, both medicinally important as dietary anticancer and antioxidant agents. They are present in a variety of foods-including fruits, vegetables, tea, wine, as well as other dietary supplements-and are responsible for various health benefits. Different quercetin and resveratrol esters of Leu/Met-enkephalin and tetrapeptide Leu-Ser-Lys-Leu (LSKL) were synthesized as model systems for monitoring the influence of the peptides on biological activity of resveratrol and quercetin. General formula of the main peptidyl-quercetin derivatives is 2-[3-(aa)n-4-hydroxyphenyl]-3,5,7-tri-hydroxy-4H-1-benzopyran-4-on, and the general formula of the main peptidyl-resveratrol derivatives is (E)-5-[4-(aa)n)styryl]benzene-1,3-diol. The antioxidant and anticancer activities of prepared compounds were investigated. Significant anticancer activity was obtained for the LSKL-based both quercetin and resveratrol derivatives. All prepared compounds exhibit antioxidant activity, in particular quercetin derivative containing Met-enkephalin.

Ethnobotany and Medicinal Plant Biotechnology: From Tradition to Modern Aspects of Drug Development.

Secondary natural products from plants are important drug leads for the development of new drug candidates for rational clinical therapy and exhibit a variety of biological activities in experimental pharmacology and serve as structural template in medicinal chemistry. The exploration of plants and discovery of natural compounds based on ethnopharmacology in combination with high sophisticated analytics is still today an important drug discovery to characterize and validate potential leads. Due to structural complexity, low abundance in biological material, and high costs in chemical synthesis, alternative ways in production like plant cell cultures, heterologous biosynthesis, and synthetic biotechnology are applied. The basis for any biotechnological process is deep knowledge in genetic regulation of pathways and protein expression with regard to todays "omics" technologies. The high number genetic techniques allowed the implementation of combinatorial biosynthesis and wide genome sequencing. Consequently, genetics allowed functional expression of biosynthetic cascades from plants and to reconstitute low-performing pathways in more productive heterologous microorganisms. Thus, de novo biosynthesis in heterologous hosts requires fundamental understanding of pathway reconstruction and multitude of genes in a foreign organism. Here, actual concepts and strategies are discussed for pathway reconstruction and genome sequencing techniques cloning tools to bridge the gap between ethnopharmaceutical drug discovery to industrial biotechnology.

Synthesis of phytochemicals-stabilized gold nanoparticles and their biological activities against bacteria and Leishmania.

Nanoscale materials have shown promising results in the field of medicine as therapeutic agents and drugs delivery vehicles. In the current study, gold nanoparticles (AuNPs) were prepared by a green and facile method using the aqueous extract of Rhazya stricta decne as a source of reducing and stabilizing agents. The bio-fabricated AuNPs were characterized by UV-visible spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM) and FTIR spectroscopy. Antimicrobial activities of the biosynthesized AuNPs were tested against Leishmania tropica (HTD7), E. coli and S. aureus. AuNPs were the most effective agents in inhibiting the growth of intra-THP-1 amastigotes at 100 µg/mL concentration (IC50 = 43 µg/mL) after 48-h incubation. In addition, the prepared AuNPs also displayed good activity against E. coli (MIC = 25.0 µg/mL) and Bacillus subtilis (50.0 µg/mL). Interestingly, biogenic AuNPs did not exhibit cytotoxic effect against the THP-1 cells after 24 h exposure. The findings of this study conclude that phytochemicals-stabilized AuNPs could be a safe and effective source of antimicrobial agents.

Facile and green synthesis of phytochemicals capped platinum nanoparticles and in vitro their superior antibacterial activity.

The increase in the severe infectious diseases and resistance of the majority of the bacterial pathogens to the available drug is a serious problem now a day. In order to overcome this problem it is necessary to develop new therapeutic agents which are non-toxic and more effective to inhibit these microbial pathogens. For this purpose the plant extract of highly active medicinal plant, Taraxacum laevigatum was used for the synthesis of platinum nanoparticles (PtNPs) to enhance its bio-activities. The surface plasmon resonance peak appeared at 283nm clearly represent the formation of PtNPs. The results illustrate that the bio-synthesized PtNPs were uniformly dispersed, small sized (2-7nm) and spherical in shape. The green synthesized PtNPs were characterized by UV-vis spectroscopy, XRD, TEM, SEM, EDX, DLS and FTIR. These nanoparticles were tested against gram positive bacteria (Bacillus subtilis) and gram negative bacteria (Pseudomonas aeruginosa). The bio-synthesized PtNPs were examined to be more effective against both of the bacteria. The results showed, that the zone of inhibition of PtNPs against P. aeruginosa was 15 (±0.5) mm and B. subtilis was 18 (±0.8) mm. The most significant outcome of this examination is that PtNPs exhibited strong antibacterial activity against P. aeruginosa and B. subtilis which have strong defensive system against several antibiotics.

Actividad cicatrizante del cremigel elaborado a base del extracto atomizado de las hojas de Solanum nitidum R.&P. "ñuñunga", Ayacucho - 2014 / Cremigel healing activity based on the atomized extract of the leaves of Solanum nitidum R. & P. "ñuñunga", Ayacucho - 2014

La búsqueda e investigación de plantas medicinales con contenidos químicos y propiedades farmacológicas que contribuyen a la cicatrización, se extraen los metabolitos responsables de dicha acción y pueden ser presentadas en formulaciones magistrales como cremas, geles, jarabes etc. La investigación es básica experimental, Solanum nitidum R. & P. "ñuñunga", fue recolectada en la comunidad de Huaraca, distrito de Vinchos, provincia de Huamanga. El objetivo de la presente investigación fue demostrar la actividad cicatrizante del cremigel elaborado a base del extracto atomizado de Solanum nitidum R. & P. "ñuñunga", su ejecución se realizó en los laboratorios de la Escuela de Formación Profesional de Farmacia y Bioquímica. Para la determinación del efecto cicatrizante se utilizó el método de Montón J. Al extracto atomizado de las hojas Solanum nitidum R. & P. "ñuñunga", se realizo la marcha fitoquimico identificando la presencia de taninos, flavonoides, saponinas, catequinas, alcaloides y quinonas; mientras que sus parámetros fisicoquímicos evaluados fueron: polvo fino color verde, sabor amargo, 7,45% de humedad, 2,24% de cenizas totales, muy solubles en agua, con un rendimiento de 9,6%. El cremigel formulado fue elaborado cumpliendo con las técnicas y procedimientos en formulación magistral dermatológica. Según Fernandez, E. De los controles se obtuvo un cremigel de color crema a marrón claro de aspecto homogéneo, poder de evanescencia y extensibilidad alta, pH entre 6,30 a 7,43, no encontrando contaminación microbiológica. El experimento se realizó con ratas wistar, a los que después de provocarles la herida de un área de 1 cm2 en el lomo del animal se aplico diariamente el cremigel formulado para ayudar a la cicatrización, luego las heridas serán fotografiadas cada dos días bajo una escala medible, estas imágenes fueron pasadas al programa de AutoCAD para su cuantificación. Las ratas fueron divididas en cinco grupos de trabajo: tres ilevaluií l.ui'ltentraciones al1%, 2% y 4% ud I,(Cilli~cl, otro grupo fue tr&táuú CÜII un estándar (Dermaclín plus®) y la última con un blanco que mostro una cicatrización normal, l. Mediante el análisis de varianza se determinó la diferencia significativa que existe entre los grupos de tratamientos (p<0.05) y con la prueba de Duncan se determinó específicamente que pruebas fueron diferentes. Se concluye que el cremigel elaborado al 1%, 2% y 4% tuvo un mejor efecto cicatrizante en comparación al estándar empleado.