Development of phospholipon®90H complex nanocarrier with enhanced oral bioavailability and anti-inflammatory potential of genistein.

Genistein (GEN), an isoflavonoid, offers multifunctional biological activities. However, its poor oral bioavailability, aqueous solubility, extensive metabolism, and short half-life restricted its clinical use. Therefore, the Phospholipon®90H complex of genistein (GPLC) was prepared to enhance its biopharmaceutical properties and anti-inflammatory activity. GPLC was characterized by employing particle size and zeta potential, Fourier transforms infrared spectrophotometry, differential scanning calorimetry, powder x-ray diffractometry, proton nuclear magnetic resonance, aqueous solubility, in vitro dissolution, ex vivo permeation, oral bioavailability and in vivo anti-inflammatory activity. The complex showed high entrapment of GEN (∼97.88% w/w) within the Phospholipon®90H matrix. Particle size and zeta potential studies confirmed the small particle size with the modest stability of GPLC. The characterization analysis supported the formation of GPLC through the participation of hydrogen bonding between GEN and Phospholipon®90H. GPLC significantly enhanced the aqueous solubility (∼2-fold) compared to GEN. Dissolution studies revealed that GPLC drastically improved the GEN dissolution rate compared to GEN. Likewise, the complex improved the permeation rate across the membrane compared to GEN. GPLC formulation significantly enhanced the oral bioavailability of GEN via improving its Cmax, tmax, AUC, half-life and mean residence time within the blood circulation compared to GEN. The GPLC (∼20 mg/kg, p.o.) remarkably inhibited the increase in paw edema up to 5 h, compared to GEN and diclofenac. Results suggest that the Phospholipon®90 complex is a superior and promising carrier for enhancing the biopharmaceutical parameters of GEN and other bioactive with similar properties.

Current Discovery Progress of Some Emerging Anti-infective Chalcones: Highlights from 2016 to 2017.

The anti-infective potentials of the natural products are very well known for centuries and are a part of traditional healing. The foremost therapeutic classes include flavones, isoflavones, flavonols, flavanones, flavanols, proanthocyanidins, anthocyanidins, chalcones, and aurones. The chalcone or 1,3-diphenyl-2E-propene-1-one represents the class of natural products which are comprised of benzylideneacetophenone function; i.e. two aromatic moieties linked together by an α, ß-unsaturated carbonyl bridge comprising three-carbons. At present, chalcone is one of the privileged scaffolds that can be synthesized in the laboratory to derive different pharmacologically active compounds. This article is the continued form of the previously published work on anti-infective perspectives of chalcones (highlighted till 2015). The current work emphasizes on the discovery process of the chalcone in the period of 2016 to 2017 on malaria, trypanosomiasis, leishmaniasis, filaria, tuberculosis, netamodes, Human Immunodeficiency Virus (HIV), Tobacco Mosaic Virus (TMV), Severe Acute Respiratory Syndrome (SARS), and miscellaneous conditions. This review comprehensively focuses on the latest progress related with the anti-infective chalcones. The content includes the crucial structural features of chalcone scaffold including structure-activity relationship(s) along with their plausible mechanism of action(s) from the duration Jan 2016 to Dec 2017. This literature will be of prime interest to medicinal chemists in getting ideas and concepts for better rational development of potential anti-infective inhibitors.

Mutant B-Raf Kinase Inhibitors as Anticancer Agents.

The Ras/Raf/MEK/ERK signaling pathway involves various kinases in which each kinase is associated with one another through signals and regulates cell proliferation, differentiation and apoptosis. This pathway is dysregulated almost in all cancers due to the amplification and genetic mutation of various components of the pathway. The genetic mutations have been reported to cause drug resistance to the current chemotherapy of melanomas. B-Raf is one of the most commonly mutated proto-oncogenes and plays a significant role in the development of numerous cancers of high clinical impact. Therefore, mutant B-Raf kinase may be a promising therapeutic target for the development of novel anticancer drugs. Many BRAF inhibitors discovered during the last decade showed promising anticancer activity, especially on tumors that harbor BRAFV600E mutations. Currently, vemurafenib and dabrafenib are USFDA approved drugs used as B-Raf inhibitors. Few drugs which are under clinical development phases such as LGX818, GDC0879, XL281, ARQ736, PLX3603 (RO5212054), and RAF265 etc. pave the path for further designing of B-Raf inhibitors. The present review focuses primarily on the Ras/Raf/MEK/ERK signaling pathway with mutant B-Raf as a therapeutic target for anticancer drug development. The essential pharmacophoric features of B-Raf inhibitors, their structure activity relationships (SARs) and molecules under clinical trials have been highlighted.