The modified steroidal alkylating agent, 17 beta-hydroxy-3-aza-A-homo-4 alpha-androsten-4-one-p-bis(2-chloroethyl)aminophenoxyacetate++ + has been tested against L1210 and P388 leukemias, and Lewis lung cancer, on DNA synthesis of EAT, L1210, P388, and BHK cell cultures, and on the induction of sister chromatid exchange. Comparable studies in vivo and in vitro were also done with p-bis(2-chloroethyl)aminophenoxyacetic acid, cyclophosphamide, melphalan, and chlorambucil.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1159/000227314 | DOI Listing |
Yakugaku Zasshi
May 2024
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.
A series of antitumor bicyclic hexapeptide RA-VII analogues modified at residue 2, 3, or 6 were prepared by the chemical transformation of the hydroxy, methoxy, or carboxy groups or the aromatic rings of natural peptides RA-II, III, V, VII, and X. Analogues with modified side chains or peptide backbones, which cannot be prepared by the chemical transformation of their natural peptides, and newly isolated peptides from Rubia cordifolia roots were synthesized by using protected cycloisodityrosines prepared by the degradation of bis(thioamide) obtained from RA-VII or the diphenyl ether formation of boronodipeptide under the modified Chan-Lam coupling reaction conditions. Studies of the conformational features of the analogues and the newly isolated peptides and their relationships with cytotoxic activities against the HCT-116, HL-60, KATO-III, KB, L1210, MCF-7, and P-388 cell lines revealed the following: the methoxy group at residue 3 is essential for the potent cytotoxic activity; the methyl group at Ala-2 and Ala-4 but not at D-Ala-1 is required to establish the bioactive conformation; the N-methyl group at Tyr-5 is necessary for the peptides to adopt the active conformation preferentially; and the orientation of Tyr-5 and/or Tyr-6 phenyl rings has a significant effect on the cytotoxic activity.
View Article and Find Full Text PDFMar Drugs
June 2022
Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki 569-1094, Osaka, Japan.
The enantiomers of 6-fluoro-, 6-bromo-, and 6-iodopericosine A were synthesized. An efficient synthesis of both enantiomers of pericoxide via 6-bromopericosine A was also developed. These 6-halo-substituted pericosine A derivatives were evaluated in terms of their antitumor activity against three types of tumor cells (p388, L1210, and HL-60) and glycosidase inhibitory activity.
View Article and Find Full Text PDFChirality
October 2022
Department of Medicinal Molecular Chemistry, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
Chiral high-performance liquid chromatography (HPLC) analysis of natural pericosine A, which appeared in literature first in 1977, from Periconia byssoides was conducted using a column CHIRALPAK® AD-H to determine the enantiomeric composition of the original mixture which was found to be 68: 32 mixtures of (+)- and (-)-enantiomer, respectively. Furthermore, two independently isolated samples of pericosine A from the same fungus were also analyzed to show the two peaks in the HPLC charts at approximate 1:1 ratio. These results concluded that pericosine A derived from Periconia byssoides was indeed an enantiomeric mixture.
View Article and Find Full Text PDFMar Drugs
March 2022
Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1, Nasahara, Takatsuki City 569-1094, Osaka, Japan.
Two new cytotoxic metabolites, halosmysins B and C, have been isolated from the fungus sp. OUPS-135D-4 separated from the marine alga These chemical structures have been elucidated by 1D and 2D NMR, and HRFABMS spectral analyses. The new compounds had the same 14-membered macrodiolide skeleton as halosmysin A, which was isolated from this fungal strain previously.
View Article and Find Full Text PDFMolecules
March 2022
JSC International Research and Production Holding "Phytochemistry", Karaganda 100009, Kazakhstan .
The sesquiterpene γ-lactone estafiatin , the molecule of which has a structure of 3,4α-epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide, is characteristic of plants of the genera L. and L. of the family.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!