Design, synthesis, docking study, α-glucosidase inhibition, and cytotoxic activities of acridine linked to thioacetamides as novel agents in treatment of type 2 diabetes.

A novel series of acridine linked to thioacetamides 9a-o were synthesized and evaluated for their α-glucosidase inhibitory and cytotoxic activities. All the synthesized compounds exhibited excellent α-glucosidase inhibitory activity in the range of IC50 = 80.0 ±â€¯2.0-383.1 ±â€¯2.0 µM against yeast α-glucosidase, when compared to the standard drug acarbose (IC50 = 750.0 ±â€¯1.5 µM). Among the synthesized compounds, 2-((6-chloro-2-methoxyacridin-9-yl)thio)-N-(p-tolyl) acetamide 9b displayed the highest α-glucosidase inhibitory activity (IC50 = 80.0 ±â€¯2.0 µM). The in vitro cytotoxic assay of compounds 9a-o against MCF-7 cell line revealed that only the compounds 9d, 9c, and 9n exhibited cytotoxic activity. Cytotoxic compounds 9d, 9c, and 9n did not show cytotoxic activity against the normal human cell lines HDF. Kinetic study revealed that the most potent compound 9b is a competitive inhibitor with a Ki of 85 µM. Furthermore, the interaction modes of the most potent compounds 9b and 9f with α-glucosidase were evaluated through the molecular docking studies.

Photocatalytic inactivation of Vibrio fischeri using Fe2O3-TiO2-based nanoparticles.

Biofouling is a major problem in water membrane processes, especially in seawater reverse osmosis plants. Inactivation of Vibrio fischeri (a well-known marine bacterium forming biofilm) through photocatalysis via visible light was investigated in this work using active Fe2O3-TiO2 nanoparticles. Five Fe2O3-TiO2 photocatalysts with different weight percentage of Fe2O3 (0-5 wt%) were synthesized using an ultrasonic-assisted co-precipitation method. The photocatalysts were characterized by powder X-ray diffraction (XRD), BET surface area, transmission electron Æ (TEM) plus selected area electron diffraction (SAED) patterns, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) and diffuse-reflectance spectroscopy (DRS). Based on the design of experiments, the synthesized photocatalysts were tested for inactivation of V. fischeri under visible light irradiation at different temperatures (25-35 °C) and different photocatalyst dosage (0.1-2 g/L). The photocatalytic microbial inactivation experiments were performed in artificial seawater appropriate for growth of the marine bacterium. The results revealed that the highest inactivation efficiency of V. fischeri was achieved when 1 g/L of 2.5 wt% Fe2O3-TiO2 were used, at 35 °C. Photocatalytic inactivation of microorganisms using visible light-driven Fe2O3-TiO2 photocatalysts, could introduce an innovative green method in pretreatment units of reverse osmosis plants to control the membrane biofouling.

Design, Synthesis, In vitro Cytotoxic Activity Evaluation, and Study of Apoptosis Inducing Effect of New Styrylimidazo[1,2-a]Pyridines as Potent Anti-Breast Cancer Agents.

BACKGROUND: This paper reports synthesis, cytotoxic activity, and apoptosis inducing effect of a novel series of styrylimidazo[1,2-a]pyridine derivatives. OBJECTIVE: In this study, anti-cancer activity of novel styrylimidazo[1,2-a]pyridines was evaluated. METHODS: Styrylimidazo[1,2-a]pyridine derivatives 4a-o were synthesized through a one-pot three-component reaction of 2-aminopyridines, cinnamaldehydes, and isocyanides in high yield. All synthesized compounds 4a-o were evaluated against breast cancer cell lines including MDA-MB-231, MCF-7, and T-47D using MTT assay. Apoptosis was evaluated by acridine orange/ethidium bromide staining, cell cycle analysis, and TUNEL assay as the mechanism of cell death. RESULTS: Most of the synthesized compounds exhibited more potent cytotoxicity than standard drug, etoposide. Induction of apoptosis by the most cytotoxic compounds 4f, 4g, 4j, 4n, and 4m was confirmed through mentioned methods. CONCLUSION: In conclusion, these results confirmed the potency of styrylimidazo[1,2-a]pyridines for further drug discovery developments in the field of anti-cancer agents.

Chemodiversity of Nepeta menthoides Boiss. & Bohse. essential oil from Iran and antimicrobial, acetylcholinesterase inhibitory and cytotoxic properties of 1,8-cineole chemotype.

The essential oil of Nepeta menthoides Boiss. & Bohse., from Iran, was analysed by GC/MS. Two types of multivariate analyses were done based on the chemical composition of the investigated sample in this study and 12 other samples reported in the literature to show the chemodiversity in essential oil composition. Antimicrobial, acetylcholinesterase inhibitory and cytotoxic activities of the essential oil and its major component were assessed. Twenty-one compounds were identified, representing 96.81% of the total oil and the major constituent was 1,8-cineole (70.06%). Multivariate analyses revealed two chemotypes, i.e. nepetalactone and 1,8-cineole. The essential oil of the sample investigated in this study which was a 1,8-cineole chemotype and 1,8-cineole showed moderate antimicrobial activity and significantly inhibited the activity of acetylcholinesterase enzyme. Cytotoxicity evaluation against three breast cancer cell lines showed a potent inhibitory activity. Further investigations are necessary to confirm the variety in several populations of N. menthoides.

A systematic review of drugs in late-stage development for the treatment of multiple sclerosis: a focus on oral synthetic drugs.

Multiple sclerosis (MS) is a heterogeneous, chronic, debilitating immune-mediated disease of the central nervous system (CNS). There are four types of MS according to their relapsing or progressive pattern that include relapsing-remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS), and progressive relapsing (PRMS). There is no definite cure for MS, thus medications typically focus on slowing the progression of the disease, managing symptoms and improving the quality of life. There is no specific medication for the management of PPMS and thus these patients are often neglected. New medicines in this phase of the disease are needed. On the other hand injectable immunomodulatory medicines, which dominated the MS market for over the past two decades, raise the issues of adherence and tolerance while oral therapies do offer a step forward in convenience. This systematic review article discusses the emerging synthetic small molecule that administered orally for MS treatment. We searched PubMed, Web of Science and Google Scholar to summaries the present knowledge on mechanism of action, and completed and current clinical trial of laquinimod, masitinib and siponimod. Data were collected from 1985 to January 2015. The development of effective medicines for MS is critically dependent upon understanding the biological basis of this complex multifactorial disease. The current pharmacotherapeuetic options for its treatment are mainly immunomodulators which were developed on the basis that MS is an autoimmune disease. The new synthetic small molecule agents such as laquinimod, masitinib and siponimod with different mechanism of actions can be administered orally rather than by injection.

Discovery Approaches for Novel Dyslipidemia Drugs.

INTRODUCTION: Dyslipidemia is increased fasting level of total cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG), along with decreased levels of HDL cholesterol (HDL-C). Owing to effect on the cardiovascular system and increased chances of metabolic diseases, it is needed to review novel under development drugs and new approaches in drug discovery for dyslipidemia. AREAS COVERED: This article reviews all phases I to IV clinical trials and preclinical trials with results associated with novel treatment of dyslipidemia. Drug discovery for dyslipidemia, toward newer targets has been addressed. FINDINGS: Statins are, currently available, best choice of drugs for treating dyslipidemia and coronary diseases. In addition to this, lipid lowering drugs support treatment to a great extent, either as monotherapy or in combinations with other groups. Pravastatin used in combination with cholesteryl ester, transfers protein inhibitors (CETP) to produce efficient results. Peroxisome proliferator-activated receptor agonists (PPAR) like muraglitazar, aleglitazar and tesaglitazar are PPAR α/γ receptor agonist, dual in action performs better in phase 3 clinical study and reduces renal and cardiovascular events. By targeting both receptors, a better treatment for cardiovascular and diabetic problems can be achieved. Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors like humanized monoclonal antibodies, are newly discovered inhibitors that reduce the risk of cardiovascular diseases. During the past few years, nucleic acid-based therapies targeting lipid and lipoprotein metabolism, such as microsomal TG transfer protein (MTP) may be a promising therapeutic approach to treat vascular diseases. Gene regulating transcription factors involved in bile acids and cholesterol metabolism can be controlled by FXR agonists in dyslipidemia. To overcome these drawbacks, many thyroid hormone analogues have been developed to lower down cholesterol level by targeting specifically thyroid hormone ß receptors abundantly present in the liver without severe side effects. Virtual screening, an important tool in screening databases of the lead compounds, provides a good platform to access new compounds. In this review, examples of novel FXR modulators, thyromimetic agents, cholesterol absorption inhibitors and other new anti hyperlipidemia scaffolds have been addressed.