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Molecules ; 26(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500603


The past few decades have witnessed significant progress in anticancer drug discovery. Small molecules containing heterocyclic moieties have attracted considerable interest for designing new antitumor agents. Of these, the pyrimidine ring system is found in multitude of drug structures, and being the building unit of DNA and RNA makes it an attractive scaffold for the design and development of anticancer drugs. Currently, 22 pyrimidine-containing entities are approved for clinical use as anticancer drugs by the FDA. An exhaustive literature search indicates several publications and more than 59 patents from the year 2009 onwards on pyrimidine derivatives exhibiting potent antiproliferative activity. These pyrimidine derivatives exert their activity via diverse mechanisms, one of them being inhibition of protein kinases. Aurora kinase (AURK) and polo-like kinase (PLK) are protein kinases involved in the regulation of the cell cycle. Within the numerous pyrimidine-based small molecules developed as anticancer agents, this review focuses on the pyrimidine fused heterocyclic compounds modulating the AURK and PLK proteins in different phases of clinical trials as anticancer agents. This article aims to provide a comprehensive overview of synthetic strategies for the preparation of pyrimidine derivatives and their associated biological activity on AURK/PLK. It will also present an overview of the synthesis of the heterocyclic-2-aminopyrimidine, 4-aminopyrimidine and 2,4-diaminopyrimidine scaffolds, and one of the pharmacophores in AURK/PLK inhibitors is described systematically.

Aurora Quinases/antagonistas & inibidores , Proteínas de Ciclo Celular/antagonistas & inibidores , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Pirimidinas/síntese química , Pirimidinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Descoberta de Drogas/métodos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
Expert Opin Drug Deliv ; 16(7): 687-699, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31111766


INTRODUCTION: Coinfection with Mycobacterium tuberculosis is the leading cause of death in HIV positive patients. In 2017, about 0.3 million HIV positive people died of tuberculosis. There is high load of mycobacteria and HIV in the lungs and eradication of the same is vital for patient survival. AREAS COVERED: This review focuses on the pathogenesis of HIV-TB coinfection and the current management approaches of this coinfection. It presents a detailed discussion of current investigations in novel drug delivery systems for effective targeting of HIV-TB lung reservoirs, especially via pulmonary drug delivery. Additionally, emphasis is given to the need of HIV-TB cotargeting, an unmet need in management of HIV-TB coinfection. EXPERT OPINION: To achieve the goal of complete eradication of HIV-TB reservoirs in lungs requires focused research strategies to be undertaken in the area of pulmonary delivery systems. These endeavors could eventually lead to better patient compliance and improved treatment outcomes. The treatment regimen of HIV-TB coinfection is associated with a major drawback of low therapeutic concentration of drugs in lungs. Nanotechnology provides an excellent platform for delivery of anti-TB and anti-HIV drugs via the pulmonary route thereby serving as a viable and effective means of managing the mycobacterial and HIV reservoirs in the lungs.

Fármacos Anti-HIV/uso terapêutico , Antituberculosos/administração & dosagem , Infecções por HIV/tratamento farmacológico , Tuberculose/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Mycobacterium tuberculosis
J Mater Sci Mater Med ; 29(12): 186, 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30523419


Rivaroxaban (RIV) is an oral anticoagulant used in the prevention of venous thromboembolism in adult patients after total hip replacement or total knee replacement surgery. It is practically insoluble in water and buffer systems (pH 3-9). The present study was aimed to investigate the ß-CD-based inclusion complexes and nanocomposites of rivaroxaban (RIV) for solubility and dissolution enhancement. A novel solubility enhancement approach of inclusion complexation of RIV with ß-CD using spray drying method combined with high pressure homogenization as a particle engineering method was used. Change in crystallinity of RIV nanocomposites was assessed by DSC and PXRD. The interaction of drug with ß-CD was projected through 1H-NMR and FT-IR studies. Saturation solubility and in vitro dissolution study revealed a dramatic increase in solubility and dissolution of RIV, respectively. Thus, spray-dried ß-CD-based nanocomposites could be an innovative approach for solubility and dissolution enhancement of RIV.

Anticoagulantes/química , Nanocompostos/química , Rivaroxabana/química , beta-Ciclodextrinas/química , Formas de Dosagem , Composição de Medicamentos , Liberação Controlada de Fármacos , Solubilidade
Int J Pharm ; 548(1): 707-720, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30012508


Dendrimers are novel polymeric nanoarchitectures characterized by hyper-branched 3D-structure having multiple functional groups on the surface that increases their functionality and make them versatile and biocompatible. Their unique properties like nanoscale uniform size, high degree of branching, polyvalency, water solubility, available internal cavities and convenient synthesis approaches make them promising agent for biological and drug delivery applications. Dendrimers have received an enormous attention from researchers among various nanomaterials. Dendrimers can be used as a carrier for diverse therapeutic agents. They can be used for reducing drug toxicities and enhancement of their efficacies. The present review provide a comprehensive outline of synthesis of dendrimers, interaction of dendrimer with guest molecules, properties, characterization and their potential applications in pharmaceutical and biomedical field.

Dendrímeros , Sistemas de Liberação de Medicamentos , Animais , Dendrímeros/administração & dosagem , Dendrímeros/química , Interações Medicamentosas , Humanos
Carbohydr Polym ; 173: 37-49, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28732878


Cyclodextrin-based nanosponges (CD-NS) are innovative cross-linked cyclodextrin polymers nanostructured within three-dimensional network. CD-NS are highly porous nanoparticles characterized by crystalline or amorphous structure, spherical shape and swelling properties. Different cross-linkers provide variety of nanosponges. The polarity, dimension of the polymer mesh and release of entrapped molecule can be easily tuned by varying the type of cross-linker and degree of cross-linking. The site-specific targeting can be achieved by conjugating various ligands on the surface of nanosponge. They offer unique advantage of controlled release and are biologically safe and biodegradable material. Cyclodextrin-based nanosponges can form complexes with different types of lipophilic or hydrophilic molecules. The nanosponges could be used to improve the aqueous solubility of poorly water-soluble molecules, protect degradable substances and as innovative carrier in pharmaceuticals, cosmetics, protein/peptide delivery, diagnostics, enzyme-catalysed reactions, environmental control and agrochemistry.