https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

(2003). Hepatotoxicity and Mechanism of Action of Haloalkanes: Carbon Tetrachloride as a Toxicological Model. Critical Reviews in Toxicology: Vol. 33, No. 2, pp. 105-136.

Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model.

Fundamental physiochemical features of CNS drugs are related to their ability to penetrate the blood-brain barrier affinity and exhibit CNS activity. Factors relevant to the success of CNS drugs are reviewed. CNS drugs show values of molecular weight, lipophilicity, and hydrogen bond donor and acceptor that in general have a smaller range than general therapeutics. Pharmacokinetic properties can be manipulated by the medicinal chemist to a significant extent. The solubility, permeability, metabolic stability, protein binding, and human ether-ago-go-related gene inhibition of CNS compounds need to be optimized simultaneously with potency, selectivity, and other biological parameters. The balance between optimizing the physiochemical and pharmacokinetic properties to make the best compromises in properties is critical for designing new drugs likely to penetrate the blood brain barrier and affect relevant biological systems. This review is intended as a guide to designing CNS therapeutic agents with better drug-like properties.

https://link.springer.com/content/pdf/10.1602/neurorx.2.4.541.pdf

Medicinal chemical properties of successful central nervous system drugs.

The known diversity of dart-poison frog species has grown from 70 in the 1960s to 247 at present, with no sign that the discovery of new species will wane in the foreseeable future. Although this growth in knowledge of the diversity of this group has been accompanied by detailed investigations of many aspects of the biology of dendrobatids, their phylogenetic relationships remain poorly understood. This study was designed to test hypotheses of dendrobatid diversification by combining new and prior genotypic and phenotypic evidence in a total evidence analysis. DNA sequences were sampled for five mitochondrial and six nuclear loci (approximately 6,100 base pairs [bp]; x¯ = 3,740 bp per terminal; total dataset composed of approximately 1.55 million bp), and 174 phenotypic characters were scored from adult and larval morphology, alkaloid profiles, and behavior. These data were combined with relevant published DNA sequences. Ingroup sampling targeted several previously unsampled species, including Ar...

Phylogenetic systematics of dart-poison frogs and their relatives (amphibia: athesphatanura: dendrobatidae)

Catalytic enantioselective allylation of carbonyl compounds and imines.

Further classification of skin alkaloids from neotropical poison frogs (dendrobatidae), with a general survey of toxic/noxious substances in the amphibia

Phosgene: a metabolite of chloroform.

Two new polycyclic guanidine alkaloids, crambescidin 826 (1) and dehydrocrambine A (2), and the known compounds crambescidin 800 (3) and fromiamycalin (4) were isolated from the marine sponge Monanchora sp. The structures of 1 and 2 were elucidated by 2D NMR and mass spectrometry, and relative stereochemistry was established by analysis of coupling constants and ROESY spectra. The pentacyclic guanidine alkaloids 1, 3, and 4 inhibit HIV-1 envelope-mediated fusion in vitro with IC(50)'s of 1-3 microM, while compound 2, a tricyclic guanidine alkaloid, showed weaker inhibition, with an IC(50) of approximately 35 microM.

Crambescidin 826 and dehydrocrambine A: new polycyclic guanidine alkaloids from the marine sponge Monanchora sp. that inhibit HIV-1 fusion.

Forty alkaloids were detected and characterized from skin extracts of high- and low-elevation populations of the poison frog Dendrobates histrionicus from northwestern Colombia. Combined gc/ms with NH3 or ND3 in a chemical ionization mode detected protonated parent ions and determined the number of exchangeable NH and OH hydrogens. Six previously unknown dendrobatid alkaloids were characterized. Two were 2,5-disubstituted pyrrolidines, which included pyrrolidine 197B, a trans-2-butyl-5-pentylpyrrolidine, while a third was a 2,6-dipentylpiperidine. Indolizidines 239AB and 239CD had the same relative configuration as the parent alkaloid 223AB [(5E,9E)3-butyl-5-propylindolizidine] and contained, respectively, a omega-hydroxy group in the propyl or butyl side chain. The profiles of alkaloids in the new northern populations of D. histrionicus are typical of the species in containing a set of about eight histrionicotoxins, in marked contrast to a related species, Dendrobates lehmanni, which does not contain histrionicotoxins.

Alkaloids from Dendrobatid Frogs: Structures of Two ω-Hydroxy Congeners of 3-Butyl-5-Propylindolizidine and Occurrence of 2,5-Disubstituted Pyrrolidines and a 2,6-Disubstituted Piperidine

Noel F. Whittaker

Papers

Further classification of skin alkaloids from neotropical poison frogs (dendrobatidae), with a general survey of toxic/noxious substances in the amphibia

Phosgene: a metabolite of chloroform.

Crambescidin 826 and dehydrocrambine A: new polycyclic guanidine alkaloids from the marine sponge Monanchora sp. that inhibit HIV-1 fusion.

Alkaloids from Dendrobatid Frogs: Structures of Two ω-Hydroxy Congeners of 3-Butyl-5-Propylindolizidine and Occurrence of 2,5-Disubstituted Pyrrolidines and a 2,6-Disubstituted Piperidine

Chemical and immunochemical studies on the structure of four snail galactans