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Prodrugs for targeted cancer therapy

Introduction: Prodrugs have been used to improve the selectivity and efficacy of cancer therapy by targeting unique abnormal markers that are overexpressed by cancer cells and are absent in normal tissues. In this context, different strategies have been exploited and new ones are being developed each year. Areas covered: In this review, an integrated view of the potential use of prodrugs in targeted cancer therapy is provided. Passive and active strategies are discussed in light of the advantages of each one and some successful examples are provided, as well as the clinical status of several prodrugs. Among them, antibody-drug conjugates (ADCs) are the most commonly used. However, several drawbacks, including limited prodrug uptake, poor pharmacokinetics, immunogenicity problems, difficulties in selective targeting and gene expression, and optimized bystander effects limit their clinical applications. Expert opinion: Despite the efforts of different companies and research groups, several drawbacks, such as the lack of relevant in vivo models, complexity of the human metabolism, and economic limitations, have hampered the development of new prodrugs for targeted cancer therapy. As a result, we believe that the combination of prodrugs with cancer nanotechnology and other newly developed approaches, such as aptamer-conjugated nanomaterials, are efficient strategies.

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Inverse electron demand diels-alder (IEDDA) reactions: Synthesis of heterocycles and natural products along with bioorthogonal and material sciences applications

In this review we chose to concentrate on the bibliography data from 2013 to 2015 (until February), related to the application of the Inverse Electron Demand Diels-Alder (IEDDA) reaction to the synthesis of heterocycles, as building blocks for natural products Moreover, the application of the IEDDA reaction to the recently developed bioorthogonal ligations (in 2008), using tetrazines moieties as the diene partners, and engineered alkenes or alkynes as dienophiles, will be detailed. The in vivo applications of the bioorthogonal liga-tions are particularly amazing and undoubtedly demonstrate the usefulness of this chemistry.

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Studies on inclusion complexes of 2-[4-(5′-benzylidene-4′-oxo-3′-phenyl thiazolidinyl-2′-imino)benzoyl]aminoimino-5-benzylidene-3-phenyl-4-thiazolidinone with ss-cyclodextrin

Thiazolidinones and its derivatives are good pharamacores and showing wide spectrum of fungicidal, antibacterial and tubercolostic activities.A series of 2-[4-(5′-benzylidene-4′-oxo-3′-phenylthiazolidinyl-2′-imino) benzoyl] aminoimino-5-benzylidene-3-phenyl-4-thiazolidinone have been synthesized starting from p-Aminobenzoic acid.To enhance the solubility of these synthesized compounds,the inclusion complexes were prepared with ss-cyclodextrin.The synthesis of compounds and their inclusion complexes have been ascertained from the changes in spectral characteristics and their analytical data.

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Multi-targeting anticancer agents: Rational approaches, synthetic routes and structure activity relationship

We live in a world with complex diseases such as cancer which cannot be cured with one-compound one-target based therapeutic paradigm. This could be due to the involvement of multiple pathogenic mechanisms. One-compound-various-targets stratagem has become a prevailing research topic in anti-cancer drug discovery. The simultaneous interruption of two or more targets has improved the therapeutic efficacy as compared to the specific targeted based therapy. In this review, six types of dual targeting agents along with some interesting strategies used for their design and synthesis are discussed. Their pharmacology with various types of the molecular interactions within their specific targets has also been described. This assemblage will reveal the recent trends and insights in front of the scientific community working in dual inhibitors and help them in designing the next generation of multi-targeted anti-cancer agents.

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STRUCTURAL CHARACTERIZATION OF SOME SUBSTITUTED AZOLIDINE MOLECULES: X-RAY PHOTOELECTRON SPECTROSCOPIC RESULTS

The electronic structure of a series of organic molecules of general formula <*>RN-(CH2)2-X-C=Y, which are also of interest in inorganic chemistry because of their properties as ligands towards metals, have been investigated by X-ray photoelectron spectroscopy.The results suggest a general picture of atomic charge distribution within the investigated molecules, and allow an assessment of the effect of the different substituent groups X, Y, R (X=NR’, O, S, CH2; Y=O, S, Se; R, R’=H, alkyl) on the electronic structure of the ligands.Satisfactory correlation is foundbetween experimental binding energies and computed CNDO/2 atomic charges, after correction for intramolecular Madelung potentials.

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Heterocyclic compounds containing nitrogen and sulfur, processes for their preparation and pharmaceutical compositions thereof

The invention relates to nitrogen- and sulfur-?containing heterocyclic compounds of the formula (I), wherein, Ar represents an optionally mono- or polysubstituted aryl or heteroaryl group;, R? represents a carbonyl or (C2 6alkenyl)-?carbonyl group;, R? represents a hydrogen atom, or a C1 6alkyl, phenyl or phenyl(C1 4alkyl) group;, R? represents a hydrogen atom or a (C1 6 alkoxy)carbonyl group;, R4 and R5, which may be the same or different, represent a hydrogen atom or a C1 6alkyl group;, R6 represents a hydrogen atom or a C1 6alkyl group or halophenyl group;, m is 0 or 1; and, n is 1 or 2,with the proviso that R? is a hydrogen atom when m is 0, and acid addition salts of the compounds of formula (I) and pharmaceutical compositions thereof. The invention also relates to processes for the preparation of these compounds. The compounds of formula (I) show a significant cerebral antihypoxic activity.

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PRODRUGS ACTIVATED BY REACTIVE OXYGEN SPECIES FOR USE IN THE TREATMENT OF INFLAMMATORY DISEASES AND CANCER

Prodrugs activated predominantly or exclusively in inflammatory tissue, more particularly prodrugs of methotrexate and derivatives thereof, which are selectively activated by Reactive Oxygen Species (ROS) in inflammatory tissues associated with cancer and inflammatory diseases, as well as method for preparing said prodrugs.

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Reactions of 2(3H)-furanones

This review article presents a systematic overview of approaches and reactivity data for 2(3H)-furanones, published from 1999 until 2018.

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Organic selenium compounds as potential chemotherapeutic agents for improved cancer treatment

Selenium(Se)-containing compounds have attracted a growing interest as anticancer agents over recent decades, with mounting reports demonstrating their high efficacy and selectivity against cancer cells. Typically, Se compounds exert their cytotoxic effects by acting as pro-oxidants that alter cellular redox homeostasis. However, the precise intracellular targets, signalling pathways affected and mechanisms of cell death engaged following treatment vary with the chemical properties of the selenocompound and its metabolites, as well as the cancer model that is used. Naturally occurring organic Se compounds, besides encompassing a significant antitumor activity with an apparent ability to prevent metastasis, also seem to have fewer side effects and less systemic effects as reported for many inorganic Se compounds. On this basis, many novel organoselenium compounds have also been synthesized and examined as potential chemotherapeutic agents. This review aims to summarize the most well studied natural and synthetic organoselenium compounds and provide the most recent developments in our understanding of the molecular mechanisms that underlie their potential anticancer effects.

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Pharmacology Profile of Recently Developed Multi-Functional Azoles; SAR-Based Predictive Structural Modification

Fungal infections have become ubiquitous diseases and their persistent nature and development of drug resistance have led to a global threat. Thereby urgent need to develop efficient antifungal agents is a must. Menace of protozoal diseases cannot be ruled out as the vaccines are not available currently and available anti-protozoal drugs are of low efficacy. Multidrug-resistant tuberculosis is responsible for the inefficient treatment of tuberculosis. Regarding cancer control, the five-membered heterocyclic compounds such as triazoles and tetrazoles are significant pharmacores that play prominent roles in drug design. In this regard, the research is being carried out in the field of drug design and synthesis considering azole-containing scaffolds as promising target molecules. In this review, the research on azoles having inhibitory properties against various disease causative factors such as fungi, protozoa, bacteria, mycobacteria, etc and various cancer cell lines is described. The whole research is classified on the basis of the type of the azole pharmacore on which the drug molecules are synthesized. The pharmacology of the designed molecules is expressed alongside emphasizing the moieties responsible for the potent activity. Besides, possible structural modification speculating higher biological properties is demonstrated based on SAR.

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