Synthesis of Flavanones via Palladium(II)-Catalyzed One-Pot ß-Arylation of Chromanones with Arylboronic Acids.

A total of 47 flavanones were expediently synthesized via one-pot ß-arylation of chromanones, a class of simple ketones possessing chemically unactivated ß sites, with arylboronic acids via tandem palladium(II) catalysis. This reaction provides a novel route to various flavanones, including natural products such as naringenin trimethyl ether, in yields up to 92%.

Feasibility of Reduced Ingot Hot-Top Height for the Cost-Effective Forging of Heavy Steel Ingots.

Feasibility studies have been performed on ingots with reduced hot-top heights for the cost-effective hot forging of heavy ingots. The quality of the heavy ingots is generally affected by internal voids, which have been known to be accompanied by inclusions and segregation. To guarantee the expected mechanical performance of the forged products, these voids should be closed and eliminated during the hot open die forging process. Hence, to effectively control the internal voids, the optimum hot-top height and forging schedules need to be determined. In order to improve the utilization ratio of ingots, the ingot hot-top height needs to be minimized. To investigate the effect of the reduced hot-top height on the forged products, shaft and bar products have been manufactured via hot forging of ingots having various hot-top heights. From the operational results, the present work suggests effective forging processes to produce acceptable shaft and bar products using ingots having reduced hot tops. The mechanical properties of shop-floor products manufactured from ingots with reduced hot tops have also been measured and compared with those of conventional ingot products.

Design, synthesis and evaluation of alkylphosphocholine-gefitinib conjugates as multitarget anticancer agents.

The evolving resistance to the currently used chemotherapeutic agents requires continuous efforts to develop new anticancer agents overcoming resistance and with lower side effects. Polypharmacology via designing a single molecule intercepting multiple signaling pathways is more effective than targeting a single one. Several alkylphosphocholines show anticancer activity via inhibition of Akt phosphorylation. On the other hand, several molecules having quinazoline scaffold elicit anticancer activity through inhibition of epidermal growth factor receptor (EGFR) tyrosine kinases. We report our efforts to develop alkylphosphocholines-gefitinib conjugates as multitarget anticancer agents. The antiproliferative activities of the newly synthesized compounds were evaluated against cell lines representing lung, breast, liver and skin cancers. In addition, the capability of the newly synthesized compounds to inhibit Akt phosphorylation and EGFR tyrosine kinases were determined. The results emphasized the influence of the linkers' length on the elicited bioactivity. The long chain linkers possessing conjugates were more active regarding both of the elicited antiproliferative effect and inhibition of Akt phosphorylation, while maintained the ability to inhibit EGFR tyrosine kinases. Their cytotoxic activities were superior or comparable to erlotinib and miltefosine.

Evaluation of the Abuse Potential of Novel Amphetamine Derivatives with Modifications on the Amine (NBNA) and Phenyl (EDA, PMEA, 2-APN) Sites.

Recently, there has been a rise in the number of amphetamine derivatives that serve as substitutes for controlled substances (e.g. amphetamine and methamphetamine) on the global illegal drug market. These substances are capable of producing rewarding effects similar to their parent drug. In anticipation of the future rise of new and similar psychoactive substances, we designed and synthesized four novel amphetamine derivatives with N-benzyl, N-benzylamphetamine HCl (NBNA) substituent on the amine region, 1,4-dioxane ring, ethylenedioxy-amphetamine HCl (EDA), methyl, para-methylamphetamine HCl (PMEA), and naphthalene, 2-(aminopropyl) naphthalene HCl (2-APN) substituents on the phenyl site. Then, we evaluated their abuse potential in the conditioned place preference (CPP) test in mice and self-administration (SA) test in rats. We also investigated the psychostimulant properties of the novel drugs using the locomotor sensitization test in mice. Moreover, we performed qRT-PCR analyses to explore the effects of the novel drugs on the expression of D1 and D2 dopamine receptor genes in the striatum. NBNA, but not EDA, PMEA, and 2-APN, induced CPP and SA in rodents. None of the test drugs have produced locomotor sensitization. qRT-PCR analyses demonstrated that NBNA increased the expression of striatal D1 dopamine receptor genes. These data indicate that NBNA yields rewarding effects, suggesting potential for abuse. Continual observation for the rise of related substances is thus strongly encouraged.

A case report of carbon monoxide poisoning induced cardiomyopathy complicated with left ventricular thrombus.

The heart and the brain, most oxygen-dependent organs, may be severely affected after carbon monoxide (CO) exposure. CO induced cardiotoxicity may occur as a consequence of moderate to severe CO poisoning, including angina attack, myocardial infarct, arrhythmias, and heart failure. We present a rare case of CO poisoning induced cardiomyopathy with left ventricular (LV) thrombus. It is thought that LV thrombus may have been caused severely decreased LV function with dyskinesis. After short-term anticoagulant therapy, echocardiography findings revealed complete recovery of LV dyskinesis and resolution of LV thrombus.