Sarvesh Paliwal

Pharmacokinetics study of arteether loaded solid lipid nanoparticles: an improved oral bioavailability in rats.

Arteether (ART), an artemisinin derivative, is a life saving drug for multiple drug resistant malaria. It has a deliverance effect in Falciparum malaria and cerebral malaria. We have prepared solid lipid nanoparticles (SLN) by high pressure homogenization (HPH) technique. ART-loaded SLN (ART-SLN) has been produced reproducibly with homogeneous particle size. ART-SLN was characterized for their size measured by Zetasizer Nano-ZS, Malvern, UK and by high resolution transmission electron microscopy (HR-TEM) and which was found to be 100 ± 11.2 nm. The maximum percentage entrapment efficiency (%EE) determined with the high-performance liquid chromatography (HPLC) has been found to be 69 ± 4.2% in ART-SLN-3. The release pattern from ART-SLN revealed that the release of ART is slow but time-dependent manner, which is desirable as it will help to protect the acid degradation of ART in stomach. The percentage cytotoxicity of blank SLN has been found within the acceptable range. The pharmacokinetics results indicated that ART-SLN-3 absorption has been significantly enhanced in comparison to ART in aqueous suspension and ART in ground nut oil (GNO) in rats. The % relative bioavailability (RB%) of ART-SLN to the ART in GNO and ART in aqueous suspension in rats was 169.99% and 7461%, respectively which was found to be significantly high in both the cases. From the results, it can be concluded that ART-SLN offers a new approach to improve the oral bioavailability of ART.

Wound-healing activity of ethanolic and aqueous extracts of Ficus benghalensis.

Wound healing is the process of repair that follows injury to the skin and other soft tissues. Following injury, an inflammatory response occurs and the cells below the dermis (the deepest skin layer) begin to increase collagen (connective tissue) production. Later, the epithelial tissue (the outer skin) is regenerated. There are three stages to the process of wound healing: inflammation, proliferation, and remodeling. Traditionally, Ficus benghalensis is used for wound healing. Since no detailed scientific data are available regarding the wound-healing activity of F. benghalensis, the present study was designed to explore the same. The wound-healing efficacy of ethanolic and aqueous extracts of F. benghalensis was evaluated in excision and incision wound models. The parameters studied include rate of wound contraction, period of complete epithelialization, and tensile strength of incision wound. Students t test was used to analyze the results obtained from the present study and P<0.05 was considered significant. Both the ethanolic and aqueous extracts of F. benghalensis were found to possess significant wound-healing activity, which was evidenced by decrease in the period of epithelialization, increase in the rate of wound contraction and skin-breaking strength. The present study has demonstrated that the ethanolic and aqueous extracts of F. benghalensis have properties that render them capable of promoting accelerated wound-healing activity compared with placebo control.

Synthesis of Pyrazole Derivatives Possessing Anticancer Activity: Current Status

Abstract Pyrazole is a versatile lead compound to design potent bioactive molecules for drug discovery and development, particularly in cancer therapy. The aim of this review is to present the most recent deeds in the field of synthetic route made for functionalized pyrazole derivatives active against cell proliferation disease. The review article covers the synthesis of 1H-pyrazole, synthesis of N-substituted pyrazoles, synthesis of pyrazolopyrazoles, and synthesis of pyrazoles fused with a naturally occurring moiety. Some of these reported compounds have passed the preclinical or initial-phase clinical trials for their anticancer activity. GRAPHICAL ABSTRACT

Pharmacophore based virtual screening, molecular docking and biological evaluation to identify novel PDE5 inhibitors with vasodilatory activity

Prompted by the role of PDE5 and its closely associated cAMP and cGMP in hypertension, we have attempted to discover novel PDE5 inhibitors through ligand based virtual screening. Rigorously validated model comprising of one HBA, one HY and one RA was used as a query to search the NCI database leading to retrieval of many compounds which were screened on the basis of estimated activity, fit value and Lipinskis violation. Selected compounds were subjected to docking studies which resulted into visualization of potential interaction capabilities of NCI compounds in line to pharmacophoric features. Finally three compounds were subjected to in vitro evaluation using the isolated rat aortic model. The results showed that all three compounds are potent and novel PDE5 inhibitors with vasodilatory activity range from 10(-2) to 10(-5) M.

Synthesis of 3-(1-alkyl/aminoalkyl-3-vinyl-piperidin-4-yl)-1-(quinolin-4-yl)-propan-1-ones and their 2-methylene derivatives as potential spermicidal and microbicidal agents ☆

A series of twenty two derivatives of 3-(1-alkyl/aminoalkyl-3-vinyl-piperidin-4-yl)-1-(quinolin-4-yl)-propan-1-one and their 2-methylene derivatives were synthesized from naturally abundant cinchonine (I). Tartarate salts of these compounds were prepared and evaluated for spermicidal activity. The most active compounds (24, 27, 34, 36, and 38) showing potent spermicidal activity were further evaluated against different strains of Trichomonas vaginalis, for antimicrobial activity, in HeLa cell lines for cytotoxicity and against Lactobacillus jensenii for eco-safety. The tartarate of 3-(1-pentyl-3-vinyl-piperidin-4-yl)-1-(quinolin-4-yl)-propan-1-one (27) was found to be more active than N-9 in spermicidal activity.

Development, characterization and toxicological evaluations of phospholipids complexes of curcumin for effective drug delivery in cancer chemotherapy

Abstract The purpose of this study was to prepare and characterize the complexes between curcumin (CU) phosphatidylcholine (PC) and hydrogenated soya phosphatidylcholine (HSPC) and to evaluate their anticancer activity. These CU–PC and CU–HSPC complexes (CU–PC-C and CU–HSPC-C) were evaluated for various physical parameters like Fourier transform infrared spectroscopy, melting point, solubility, scanning electron microscopy and the in vitro drug release study. These data confirmed the formation of phospholipids complexes. The in vitro hemolysis study showed that the complex was non-hemolytic. The anti-cancer potential of the complexes was demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay in MCF-7 cell line. This increase may be due to the amphiphilic nature of the complexes, which significantly enhances the water and lipid solubility of the CU. Unlike the free CU (which showed a total of only 90% drug release at the end of 8 h), complex showed around 40–60% release at the end of 8 h in dissolution studies. It showed that (when given in equimolar doses) complexes have significantly decreased the amount of CU available for absorption as compared with CU-free drug. Both CU-PC-C and CU-HSPC-C were found to be non-toxic at the dose equivalent to 2000 mg/kg of body weight of CU in the toxicity study. Acute and subacute toxicity studies confirmed the oral safety of the formulation. A series of genotoxicity studies was conducted, which revealed the non-genotoxicity potential of the developed complexes. Thus, it can be concluded that the phospholipid complexes of CU may be a promising candidate in cancer therapy.

Quantitative structure activity relationship analysis of angiotensin II AT1 receptor antagonists

The quantitative structure activity relationship (QSAR) models were developed using multiple linear regression (MLR) and partial least square (PLS) for a set of 85 AT1 receptor antagonists of hydantoin series. The MLR and PLS generated comparable models with good predictive ability and all the other statistical values, such as r, r2,

Anticancer Activity of Pyrazole via Different Biological Mechanisms

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