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4-Ethoxycarbonyl(cyano)-1,3-dimethyl-β-carbolines were synthesized via thermolysis of 4-aryl-3(5)-azidopyridines and their optical and hypoglycemic properties were studied. For the first time, the accessible Hantzsch nitropyridines were used as the starting materials. Diazotization of 3-aminopyridines having a trimethoxyaryl substituent at the C-4 position of the pyridine ring by intramolecular azo coupling afforded 7,8,9-trimethoxy-2,4-dimethylpyrido[3,4-c]cinnolines. When evaluating the hypoglycemic properties of the four obtained β-carbolines, it was found that ethyl 7-fluoro-1,3-dimethyl-9H-pyrido[3,4-b]indole-4-carboxylate, the structure of which contains the fluorine atom, has the highest glucose-lowering action. [ABSTRACT FROM AUTHOR]

Abstract Cancer is a leading cause of death generally, and to overcome this problem the introduction of a new drug developing is a continuous endeavour. An alkaloid, norharmane and its derivatives, which have anticancer activities, widely distributed in several living and synthetic chemical sources. Herewith, the suggested mechanisms of organic reactions and synthetic approaches of norharmane available so far were considered. Active sites of norharmane nucleus positions, C-1, C-3, and N-9, were used for developing new molecules and based on structure activity relationship (SAR), those have been seen with anticancer activities. This review summarizes on chemistry of synthetic strategies of norharmane derivatives, which may provide a framework to design a novel anticancer drug, in future. Graphical abstract Image 1 Highlights • The review emphasized on synthetic method approach of norharmane and its derivatives. • Anticancer activity of lead molecule from several prescribed schemes. • Elaborated on SAR of norharmane nucleus. [ABSTRACT FROM AUTHOR]

The photochemical and photophysical properties of [(nHo)Re(CO) 3 (L)] + complexes, where nHo = 9H-pyrido[3,4-b]indole and L = 2,2′ bipyridine (bpy), 1,10 phenantroline (phen) or dipyridil[3,2-a:2′3′-c]phenazine (dppz) were investigated by Laser Flash Photolysis (LFF) and Pulse Radiolysis (PR) techniques. While complexes with L = bpy or phen show absorption transients compatible with MLCT Re→L excited states, [(nHo)Re(CO) 3 (dppz)] + showed an excited state assignable to a dppz-centered, 3 ππ* dppz . In aqueous solutions, the last complex does not generate any absorption transient. However, when Calf thymus DNA was added, the same absorption spectrum was obtained. These results suggest that this complex can intercalate into DNA. The species generated in either reductive or oxidative conditions in LFF experiments were compared with those obtained in PR. Also, the quenching rate constants ( k q ) of the excited states with MV 2+ were calculated. The intercalation of the [(nHo)Re(CO) 3 (dppz)] + into DNA, increases k q ∼100 times. This result is rationalized in terms of the conditions created by the intercalation using the biopolymer as a well-organized matrix. [ABSTRACT FROM AUTHOR]

New first-row transition-metal compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) are reported. The compounds have the general formula [M(LL)(Hnor)(NO 3 ) 2 ](MeOH) 0-1 (M=Co, Ni, Cu, Zn; LL=2,2'-bipyridyl (bpy), 1,10-phenanthroline (phen)) and have been characterized by physical and analytical methods. X-ray structural analysis revealed that the compound of formula [Cu(phen)(Hnor)(NO 3 ) 2 ], (1) has a distorted 6-coordinated octahedrally-based geometry, with a planar-based [CuN 3 O] core, where Cu-L varies between 1.99 and 2.04Å and two weak axial CuO contacts (2.209 and 2.644Å) from two different nitrates. Based on spectroscopic similarities, the other compounds appear to have the same or very similar coordination geometries. The compounds showed clear cell growth inhibitory effects in two different cancer cell lines in vitro, with the copper and zinc complexes being the most toxic and in fact almost comparable to cisplatin. Flow-cytometry analysis confirmed induction of apoptosis in cancer cells treated with the compounds. Interestingly, co-incubation of the cells with metal complexes and CuCl 2 induced an increase in the cytotoxic effects, most likely due to the conversion of the metal compounds in the corresponding, and most active, copper analogues., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Four different-anion Ag(I) compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) and having the general formula [Ag(Hnor)2](anion) (anion=ClO4(-), NO3(-) and BF4(-)) [Ag(Hnor)2(MeCN)](PF6) are reported, and studied in detail regarding their coordination mode and in vitro antiproliferative effects. X-ray structural analysis revealed that the complex with the PF6(-) anion has a MeCN solvent molecule weakly coordinated to Ag(I), making the metal coordination T-shaped, while the other compounds present the classical linear Ag(I) coordination. The compounds showed certain cell growth inhibitory effects in two different cancer cell lines, with the perchlorate containing complex being the most toxic and in fact comparable to cisplatin. Notably, the compounds are stable in visible light; and the luminescence in the solid state was found to be extremely weak, whereas in MeOH solution all compounds show a moderate to weak emission band at 375 nm, when excited at 290 nm., (Copyright © 2014 Elsevier Inc. All rights reserved.)

During grilling of the roast beef the following heterocyclic aromatic amines were found: IQ=200.6 ng 100g(-1), MeIQx=719.8 ng 100 g(-1), MeIQ=532.9 ng 100g(-1), 4.8-diMeIQx=755.4 ng 100 g(-1), norharmane=507.0 ng 100 g(-1), harmane=1952.6 ng 100 g(-1), Phe-P 1=263.7 ng 100 g(-1), Trp-P 2=559.2 ng 100 g(-1), PhIP=1179.8 ng 100 g(-1) and AαC=51.7 ng 100g(-1). Their content was tested by using the method based on alkaline hydrolysis of the sample and the method based on solvent extraction of the grilled meat samples at different temperatures (without hydrolysis). The study showed that the heterocyclic aromatic amines produced during the grilling of beef are in a free form and chemically or physico-chemically bonded. The chemical forms of HAA formed in food have never been studied. For the purpose of the partial confirmation that HAA may be chemically or physico-chemically bonded, grilled beef samples were digested in vitro in model segments of the human digestive tract. Digestive enzymes, particularly proteolytic enzymes caused a statistically significant increase of free HAA determined by using solvent extraction without prior chemical hydrolysis of the sample., (Copyright © 2013 Elsevier Ltd. All rights reserved.)