Synthesis of Analogues of Flazin, in Particular, Flazinamide, as Promising Anti‐HIV Agents

Tang, Jie; Wang, Yunhua; Wang, Ruirui; Dong, Zhibao; Yang, Liu‐Meng; Zheng, Yong‐Tang; Liu, Ji‐Kai

doi:10.1002/cbdv.200890044

Cited by 59 publications

(44 citation statements)

References 26 publications

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“…Both naturally occurring and chemically synthesized β-carbolines exhibited good activities against a set of virus, such as human immunodeficiency virus (HIV) [26,48], herpes simplex virus (HSV) [27,49], vaccinia virus [50], vesicular stomatitis virus [50,51], poliovirus [49], and influenza A and B virus [51]. It was reported that the derivatives with the oxathiazepine 7-membered ring showed potential activities against influenza A and B [51].…”

Section: Resultsmentioning

confidence: 99%

Alkaloids from the Mangrove-Derived Actinomycete Jishengella endophytica 161111

et al. 2014

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A new alkaloid, 2-(furan-2-yl)-6-(2S,3S,4-trihydroxybutyl)pyrazine (1), along with 12 known compounds, 2-(furan-2-yl)-5-(2S,3S,4-trihydroxybutyl)pyrazine (2), (S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (3), (S)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (4), (4S)-4-(2-methylbutyl)-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (5), (S)-4-benzyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (6), flazin (7), perlolyrine (8), 1-hydroxy-β-carboline (9), lumichrome (10), 1H-indole-3-carboxaldehyde (11), 2-hydroxy-1-(1H-indol-3-yl)ethanone (12), and 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (13), were isolated and identified from the fermentation broth of an endophytic actinomycetes, Jishengella endophytica 161111. The new structure 1 and the absolute configurations of 2–6 were determined by spectroscopic methods, J-based configuration analysis (JBCA) method, lactone sector rule, and electronic circular dichroism (ECD) calculations. Compounds 8–11 were active against the influenza A virus subtype H1N1 with IC50 and selectivity index (SI) values of 38.3(±1.2)/25.0(±3.6)/39.7(±5.6)/45.9(±2.1) μg/mL and 3.0/16.1/3.1/11.4, respectively. The IC50 and SI values of positive control, ribavirin, were 23.1(±1.7) μg/mL and 32.2, respectively. The results showed that compound 9 could be a promising new hit for anti-H1N1 drugs. The absolute configurations of 2–5, 13C nuclear magnetic resonance (NMR) data and the specific rotations of 3–6 were also reported here for the first time.

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Section: Resultsmentioning

confidence: 99%

Alkaloids from the Mangrove-Derived Actinomycete Jishengella endophytica 161111

et al. 2014

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“…Purity of over 95% was confirmed by elemental analysis with a Perkin Elmer 2400 Series II CHNS/O organic elemental analyzer (Perkin Elmer Inc., Waltham, MA, USA). The compound 7 was prepared according previously published procedures (Tang, et al 2008) to yield off white solid, 23 mg (97%). 1 H NMR ((CD 3 ) 2 SO):  ppm 11.15 (s, 1 H), 8.28-8.08…”

Section: Synthesis Of Amino Acid Derivativesmentioning

confidence: 99%

Structural properties for selective and efficient l-type amino acid transporter 1 (LAT1) mediated cellular uptake

Kärkkäinen

Gynther

Kokkola

et al. 2018

International Journal of Pharmaceutics

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l-Type amino acid transporter 1 (LAT1) is a sodium-independent exchanger transporting large neural amino acids and several amino-acid mimicking drugs across the cell membranes. LAT1 is highly expressed at the blood brain barrier (BBB) and in numerous cancer cells and is therefore a potential drug target. However, structural features affecting the ability to bind to LAT1 and the cellular translocation by LAT1 are unclear. In the present study we determined the binding to and transport through human LAT1 of several compounds into the human breast adenocarcinoma cells (MCF-7). We show that the meta-conjugation of l-phenylalanine increases binding to human LAT1 compared to para-conjugation or aliphatic amino acid moiety. Furthermore, large, rigid and aromatic meta-substituted l-phenylalanine derivative enabled selective and efficient LAT1-mediated cellular uptake. Our results also demonstrates that in addition to binding studies, it is of utmost importance to determine the cellular accumulation of compounds. It provides crucial information on transport efficiency and selectivity of transport mechanisms that the compounds are able to utilize. Overall, these structural findings and the methodology used herein are exploitable to design LAT1-utilizing compounds, such as markers for cancer imaging and drug molecules, enabling more effective and safer treatments for cancer in the future.

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“…Flazin, a b-carboline alkaloid isolated of Suillus granulatus was found to possess anti-HIV activity [7]. A structure-activity study on 46 flazin synthesized analogues showed a potent anti-HIV activity for flazinamide, which was considered a promising anti-HIV agent [8]. Synthetic b-carboline derivatives bearing a guanidinium groupterminated side chain at C-3 exhibited anti-HIV activity in MT4 cells, inhibiting HIV replication by interfering with TAT-TAR interaction [9].…”

Section: Introductionmentioning

confidence: 99%