Molecular modeling of 3-arylisoquinoline antitumor agents active against A-549. A comparative molecular field analysis study

Molecular Design, Synthesis and Docking Study of Alkyl and Benzyl Derivatives of Robustic Acid as Topoisomerase I Inhibitors

“…To determine Topo I catalytic activity, assays were performed with supercoiled pBR32 DNA as the substrate, according to a reported protocol . Topo I and pBR322 were purchased from Takara Bio Inc. One unit of enzyme was defined as the amount that completely relaxes 0.5 μg of supercoiled pBR322 DNA in 30 min at 37 °C.…”

“…To determine Topo I catalytic activity, assays were performed with supercoiled pBR32 DNA as the substrate, according to a reported protocol. [23] Topo I and pBR322 were purchased from Takara Bio Inc. One unit of enzyme was defined as the amount that completely relaxes 0.5 μg of supercoiled pBR322 DNA in 30 min at 37°C. The reaction mixture (20 μL) was mixed with 2 μL 10 × reaction buffer solution (500 mM KOAc, 200 mM Tris-AcOH buffer, 100 mM Mg(OAc) 2 , 1 mg/mL bovine serum albumin (BSA)), 0.5 μg pBR322 DNA, 2 μL of respective compounds and then constant volume was made up to 19 μL using distilled water.…”

Development of 3-aryl-1-isoquinolinamines as potent antitumor agents based on CoMFA

“…However, we did not develop any compounds that surpassed the activity of the original hit compound 5, which was found during the natural alkaloid synthesis [6]. Our research then focused on developing potent water-soluble 3-arylisoquinolines by applying a previously constructed CoMFA model; our former CoMFA model provided significantly high cross-validated r 2 (q 2 ) value of 0.715 as well as a high conventional r 2 value of 0.927 [7]. To date, most of the CoMFA studies on diverse molecules have provided reasonable statistical values that could explain the biological activities, but application of CoMFA for finding novel bioactive compound has been rare [2].…”

“…Moreover, cell cycle dynamics analyses with apoptotic induction studies were performed because the mode of action of 3-aryl-1-isoquinolinamines remained unclear; some molecules were suggested to be partial inhibitors of topoisomerase I. The CoMFA QSAR model was constructed from 58 diverse substituted 3-arylisoquinolines with varied cytotoxicities as shown in Table 1 [7]. The steric and electrostatic contributions to the equation were 40.1 and 59.9%, respectively, and the reasonable F value (96.804) with low standard deviation value (0.251) suggested its potential for application.…”

Rhodium(I)‐Catalyzed Redox‐Economic Cross‐Coupling of Carboxylic Acids with Arenes Directed by N‐Containing Groups

“…[11] In this article, we reported a new method to carry out the pseudo-decarboxylative coupling of carboxylic acids with arenes in the absence of heavy metal oxidants, thus offering a new convenient pathway for the construction of C sp 2 À C sp 2 bonds of biaryls and C sp 3 À C sp 2 bonds of alkyl aryls, which are potentially useful for the synthesis of a vast number of nature products and bioactive compounds. [12] In general, different strategies have been proposed to facilitate the C À H activation to form C À M intermediates. [13] For oxidative decarboxylative coupling with arenes, previous efforts indicated that high-valent transition-metal species are efficient catalysts, and derive from an electrophilic metalation with relatively electron-rich arenes.…”