Exploring the Molecular Structural Requirements of Flavonoids as Beta- Secretase-1 Inhibitors Using Molecular Modeling Studies.

Background: BACE1 (beta-site amyloid precursor protein (APP) cleaving enzyme) is a key target for Alzheimer's disease research because it catalyses the rate-limiting step in the formation of amyloid protein (Aβ). Natural dietary flavonoids have gained a lot of interest as potential Alzheimer's therapy candidates because of their anti-amyloidogenic, antioxidative, and anti-inflammatory properties. More research is needed, however, to learn more about the specific routes through which flavonoids may have neuroprotective benefits in Alzheimer's disease.

Synthesis and Anticancer Activity of Thiadiazole Containing Thiourea, Benzothiazole and Imidazo[2,1-b][1,3,4]thiadiazole Scaffolds.

Background: A great array of nitrogen-containing heterocyclic rings were being extensively explored for their functional versatility in the field of medicine, especially in anticancer research. 1,3,4- thiadiazole is one of such heterocyclic rings with promising anticancer activity against several cancer cell lines, inhibiting diverse biological targets.

Introduction: The 1,3,4-thiadiazole, when equipped with other heterocyclic scaffolds, has displayed enhanced anticancer properties.

A review of pharmacological and clinical studies on the application of Shenling Baizhu San in treatment of Ulcerative colitis.

Ethnopharmacological Relevance: The prescription of Shenling Baizhu San (SLBZS) was derived from the Song Dynasty "Taiping Huimin Heji Ju Fang", which was a representative prescription for treating spleen asthenic diarrhea. The prescription comprised of 10 herbs for treating weak spleen and stomach. It describes symptoms like eating less, loose stools, cough, shortness of breath and tired limbs.

Aromatase Inhibitors Evolution as Potential Class of Drugs in the Treatment of Postmenopausal Breast Cancer Women.

Aromatase inhibitors are class of drugs that inhibit aromatase, a rate limiting enzyme in the biosynthesis of estrogens from their corresponding androgens. Estrogens play a vital role in the development and growth of breast tumors especially in postmenopausal women apart from their important functions in cell homeostasis. The reduction of estrogen physiological concentration through aromatase inhibition is one of the most important therapeutic strategies against this cancer type.

Polymeric micelles: Basic research to clinical practice.

Rapidly developing polymeric micelles as potential targeting carriers has intensified the need for better understanding of the underlying principles related to the selection of suitable delivery materials for designing, characterizing, drug loading, improving stability, targetability, biosafety and efficacy. The emergence of advanced analytical tools such as fluorescence resonance energy transfer and dissipative particle dynamics has identified new dimensions of these nanostructures and their behavior in much greater details. This review summarizes recent efforts in the development of polymeric micelles with respect to their architecture, formulation strategy and targeting possibilities along with their preclinical and clinical aspects.

In silico Evidence for Binding of Pentacyclic Triterpenoids to Keap1-Nrf2 Protein-Protein Binding Site.

Aim And Objective: Kelch like ECH-associated protein 1 (Keap1) and Nuclear factor-E2 related factor 2 (Nrf2) binding is a key step in the ubiquitination and degradation of Nrf2. The compounds inhibiting this binding exert antioxidant actions. Naturally occurring pentacyclic triterpenoids (PTs) and their synthetic derivatives are projected as activators of Nrf2 signalling.

Controlled release of therapeutics using interpenetrating polymeric networks.

Introduction: The ever-increasing developments in pharmaceutical formulations have led to the widespread use of biodegradable polymers in various forms and configurations. In particular, interpenetrating network (IPN) and semi-IPN polymer structures that are capable of releasing drugs in a controlled manner have gained much wider importance in recent years.

Areas Covered: Recently, IPNs and semi-IPNs have emerged as innovative materials of choice in controlled release (CR) of drugs as the release from these systems depends on pH of the media and temperature in addition to the nature of the system.

Design, synthesis and evaluation of small molecule imidazo[2,1-b][1,3,4]thiadiazoles as inhibitors of transforming growth factor-β type-I receptor kinase (ALK5).

A new series of imidazo[2,1-b][1,3,4]thiadiazoles 5(a-g), 6(a-g), 9(a-i) and 12(a-h) were synthesized as transforming growth factor-β (TGF-β) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-β -induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. Compound 6d, 2-(5-((2-cyclopropyl-6-(4-fluorophenyl) imidazo [2,1-b][1,3,4]thiadiazol-5-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl) acetic acid, shows prominent ALK5 inhibition (IC50 = 0.

In vitro anti cancer activity of ethanol extract fractions of Aerva lanata L.

To explore in vitro anticancer potential of Aerva lanata L. (flowering aerial part). The study was performed with 5 different human cell lines for the study of lung, leukaemia, prostate, colon and cervix cancer by using Sulphorhodamine B (SRB) assay.

2,5,6-trisubstituted imidazo[2,1-b][1,3,4]thiadiazoles: search for antihyperlipidemic agents.

A novel series of 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]thiadiazoles 4(a-d) and 7(a-i) were rationally designed through QSAR based pharmacophore approach and synthesized from 5-(1,3-benzodioxol-5-yl)-[1,3,4]thiadiazol-2-amine (1). The structures of these compounds were established by IR, (1)H NMR, (13)C NMR, HRMS technique. All the compounds were evaluated for their in vitro antihyperlipidemic activity using trition induced hyperlipidemic model.

Immunomodulatory activity of butanol fraction of Gentiana olivieri Griseb. on Balb/C mice.

Objective: To explore the immunomodulatory properties of 80% ethanol extract and butanol fraction of Gentiana olivieri (G. olivieri) Griseb on Balb/C mice.

Methods: The study was performed with basic models of immunomodulation such as the humoral antibody response (hemoglutination antibody titres), cell mediated immune response (delayed type hypersensitivity and in vivo carbon clearance or phagocytosis).

2,6-Disubstituted imidazo[2,1-b][1,3,4]thiadiazoles: search for anticancer agents.

In this study, some novel 2,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazoles 4 (a-i), 7 (a-p) and 11 (a-i) were synthesized from 5-substituted-1,3,4-thiadiazol-2-amine. The newly synthesized compounds 4a, 4b, 4c, 4e, 4g, 7j, 7l, 11b and 11c were evaluated in the National Cancer Institute for single dose in vitro primary cytotoxicity assay. Among the tested nine compounds, compound 4b (107166/760239) and 4c (107168/760240) were passed the criteria for activity in this assay and scheduled automatically for evaluation against the full panel of 60 human tumor cell lines at a minimum of five concentrations at 10-fold dilutions.

Benzothiazoles: search for anticancer agents.

Novel derivatives of 2-amino benzothiazoles 4(a-j) have been synthesized and tested for their antitumor activity using National Cancer Institute (NCI) disease oriented antitumor screen protocol against nine panel of cancer cell lines. Among the synthesized compounds, two compounds were granted NSC code and screened at National Cancer Institute (NCI)-USA for anticancer activity at a single high dose (10(-5) M) and five dose in full NCI 60 cell panel. Among the selected compounds, 7-chloro-N-(2,6-dichlorophenyl)benzo[d]thiazol-2-amine (4i) with GI(50) values of 7.

A QSAR analysis of 2-phenoxy-N-substituted acetamide analogues as hypoxia-inducible factor-1(HIF-1) inhibitors: a rational approach to anticancer drug design.

A set of thirty one substituted 2-phenoxy-N-phenylacetamide derivatives with HIF-1 inhibitory activities was subjected to 2D and 3D Quantitative Structure Activity Relationship (QSAR) studies using various combinations of descriptors. 2D-QSAR was performed using Multiple Linear Regression (MLR), Principal Component Regression (PCR) and Partial Least Squares Regression (PLS) methods. Among these three methods Multiple Linear Regression (MLR) led to the statistically significant best 2D-QSAR Model-I having correlation coefficient r(2) = 0.

Quantification of Oleanolic acid in the flower of Gentiana olivieri Griseb. by HPLC.

High Performance Liquid Chromatography (HPLC) method is a potent analytical technique for determining phytoconstituents even in minute quantities particularly that are generally present in traces concentrations in medicinal plants. The concentration of oleanolic acid (OA) in the Gentiana olivieri Griseb.(GOG) flowers is quantitatively determined by a simple, precise and accurate HPLC method.

Synthesis and anticancer evaluation of novel 2-cyclopropylimidazo[2,1-b][1,3,4]-thiadiazole derivatives.

A series of 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]-thiadiazole derivatives 4(a-k) have been prepared by reaction of 2-amino-5-cyclopropyl-1,3,4-thiadiazole and an appropriate phenacyl bromide. Further 5-bromo 5(a-k) and 5-thiocyanato 6(a-k) derivatives were synthesized in order to study the effect of these substituents on antitumor activity. Structures of these compounds were established by IR, (1)H NMR, (13)C NMR and Mass spectroscopy.

A comparative QSAR analysis of quinazoline analogues as tyrosine kinase (erbB-2) inhibitors.

In this paper, an attempt was made to develop a Quantitative Structure Activity Relationship (QSAR) model on a series of quinazoline derivatives acting as Protein tyrosine kinases (erbB-2) inhibitors using Multiple Linear Regression, Principal Component Regression and Partial Least Squares Regression methods. Among these three methods, Multiple Linear Regression (MLR) method has come out with a very promising result as compared to other two methods. Various 2D descriptors were calculated and used in the present analysis.

Synthesis and in vitro antitumor activity of substituted quinazoline and quinoxaline derivatives: search for anticancer agent.

The synthesis of some 2-furano-4(3H)-quinazolinones, diamides (open ring quinazolines), quinoxalines and their biological evaluation as antitumor agents using National Cancer Institute (NCI) disease oriented antitumor screen protocol are investigated. Among the synthesize compounds, seventeen compounds were granted NSC code and screened at National Cancer Institute (NCI), USA for anticancer activity at a single high dose (10(-5) M) in full NCI 60 cell panel. Among the selected compounds, 3-(2-chloro benzylideneamine)-2-(furan-2-yl) quinazoline-4(3h)-one 21 was found to be the most active candidate of the series at five dose level screening against Ovarian OVCAR-4 and Non-small cell lung cancer NCI-H522 with GI50 1.

3d QSAR studies on a series of quinazoline derrivatives as tyrosine kinase (egfr) inhibitor: the k-nearest neighbor molecular field analysis approach.

Epidermal growth factor receptor (EGFR) protein tyrosine kinases (PTKs) are known for its role in cancer. Quinazoline have been reported to be the molecules of interest, with potent anticancer activity and they act by binding to ATP site of protein kinases. ATP binding site of protein kinases provides an extensive opportunity to design newer analogs.

Synthesis and antimicrobial activity of 7-(2-substituted phenylthiazolidinyl)-benzopyran-2-one derivatives.

A series of 7-(2-substituted phenylthiazolidinyl)-benzopyran-2-one derivatives have been synthesized by reaction of 7-amino-4-methyl-benzopyran-2-one (1) with an appropriate substituted aldehydes to obtain various Schiff bases (3a-k) which on treatment with thioglycolic acid afforded the title compounds (4a-k). Purity of the compounds has been confirmed by TLC. Structure of these compounds were established on the bases IR, 1H NMR, 13C NMR and Mass spectral data.

Synthesis and biological evaluation of 2-trifluoromethyl/sulfonamido-5,6-diaryl substituted imidazo[2,1-b]-1,3,4-thiadiazoles: a novel class of cyclooxygenase-2 inhibitors.

A series of 2-trifluoromethyl/sulfonamido-5,6-diarylsubstituted imidazo[2,1-b]-1,3,4-thiadiazole derivatives 15a-j have been synthesized by the reaction of 2-amino-5-trifluoromethyl/sulfonamido-1,3,4-thiadiazoles 14a-b and appropriately substituted alpha-bromo-1,2-(p-substituted)diaryl-1-ethanones 13a-h. Structures of these compounds were established by IR, (1)H NMR, (13)C NMR, Mass, and HRMS data. The selected compounds were evaluated for their preliminary in vitro cyclooxygenase inhibitory activity against COX-2 and COX-1enzymes using colorimetric method.

Synthesis and anti-tubercular activity of a series of 2-sulfonamido/trifluoromethyl-6-substituted imidazo[2,1-b]-1,3,4-thiadiazole derivatives.

A series of 2-sulfonamido/trifluoromethyl-6-(4'-substituted aryl/heteroaryl)imidazo[2,1-b]-1,3,4-thiadiazole derivatives (II) have been synthesized by reaction of 2-amino-5-sulfonamido/trifluoromethyl-1,3,4-thiadiazoles and an appropriate alpha-haloaryl/heteroaryl ketones. Further 5-bromo (III), 5-thiocyanato (IV), 5-gaunylhydrazone (V) derivatives were synthesized in order to study the effect of these substituents on biological activity. Structures of these compounds were established by IR, (1)H NMR, (13)C NMR, Mass and HRMS.