Invasive fungal infections with primary and opportunistic mycoses have become increasingly common in recent years and pose a major diagnostic and therapeutic challenge. They represent a major area of concern in today's medical fraternity. The occurrence of invasive fungal diseases, particularly in AIDS and other immunocompromised patients, is life-threatening and increases the economic burden. Apart from the previously known polyenes and imidazole-based azoles, newly discovered triazoles and echinocandins are more effective in terms of specificity, yet some immunosuppressed hosts are difficult to treat. The main reasons for this include antifungal resistance, toxicity, lack of rapid and microbe-specific diagnoses, poor penetration of drugs into sanctuary sites, and lack of oral or intravenous preparations. In addition to combination antifungal therapy, other novel antimycotic treatments such as calcineurin signaling pathway blockers and vaccines have recently emerged. This review briefly summarizes recent developments in the pharmacotherapeutic treatment of invasive fungal infections.
C-H activation is a versatile tool for appending aryl groups to aromatic systems. However, heavy demands on multiple catalytic cycle operations and site-selectivity have limited its use for graphene segment synthesis. A Pd-catal- yzed one-step synthesis of functionalized triphenylene frameworks is disclosed, which proceeds by 2- or 4-fold C-H arylation of unactivated benzene derivatives. A Pd (dibenzylideneacetone) catalytic system, using cyclic diaryliodonium salts as π-extending agents, leads to site-selective inter- and intramolecular tandem arylation sequences. Moreover, N-substituted triphenylenes are applied to a field-effect transistor sensor for rapid, sensitive, and reversible alcohol vapor detection.
A simple, green and efficient method has been developed for the synthesis of biologically and materially important dihydrobenzo/naphtho[e]-1,3-oxazines in good to excellent yields through a Mannichtype condensation cyclization reaction of aromatic alcohols with HCHO and primary amines in aqueous media at ambient temperature.
Impairing the division of cancer cells with genotoxic small molecules has been a primary goal to develop chemotherapeutic agents. However, DNA mismatch repair (MMR)-deficient cancer cells, are resistant to most conventional chemotherapeutic agents. Here we have identified baicalein as a small molecule that selectively kills MutSα-deficient cancer cells. Baicalein binds preferentially to mismatched DNA and induces a DNA damage response in a mismatch repair-dependent manner. In MutSα-proficient cells, baicalein binds to MutSα to dissociate CHK2 from MutSα leading to S phase arrest and cell survival. In contrast, continued replication in the presence of baicalein in MutSα-deficient cells results in a high number of DNA double-strand breaks and ultimately leads to apoptosis. Consistently, baicalein specifically shrinks MutSα-deficient xenograft tumors and inhibits the growth of AOM-DSS-induced colon tumors in colon-specific MSH2 knockout mice. Collectively, baicalein offers the potential of an improved treatment option for patients with tumors with a DNA MMR deficiency.
CÀHactivation is aversatile tool for appending aryl groups to aromatic systems.H owever,h eavy demands on multiple catalytic cycle operations and site-selectivity have limited its use for graphene segment synthesis.AP d-catalyzed one-step synthesis of functionalized triphenylene frameworks is disclosed, which proceeds by 2-or 4-fold CÀHa rylation of unactivated benzene derivatives.A Pd 2 (dibenzylideneacetone) 3 catalytic system, using cyclic diaryliodonium salts as p-extending agents,l eads to site-selective inter-a nd intramolecular tandem arylation sequences.M oreover,N -substituted triphenylenes are applied to af ield-effect transistor sensor for rapid, sensitive,a nd reversible alcohol vapor detection.Scheme 1. Synthesis of triphenylene frameworks.
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