Sulfonated naphthyl porphyrins as agents against HIV-1.
Sulfonated 5,10,15,20-tetra(1-naphthyl)porphyrin (T1NapS) and 5,10,15,20-tetra(2-naphthyl)porphyrin (T2NapS) and their copper and iron chelates show activity against the human immunodeficiency virus (HIV-1). The porphyrins were prepared by sulfonation of the parent structures with sulfuric acid. More highly sulfonated structures were prepared by sulfonation for longer times. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry showed species with as many as eight sulfonates. Some of the mass spectral peaks for the copper chelates were consistent with loss of water, apparently from intramolecular sulfone formation between two adjacent naphthalene rings that took place during copper insertion. The compounds could be separated using capillary electrophoresis; addition of beta- or gamma-cyclodextrin gave substantially better separation of the components. Activity against HIV was evaluated using an epithelial HeLa-CD4-CCR5 cell line; EC50 values for HIV-1 IIIB and HIV-1 JR-FL ranged from 1 to 15 microg/ml. The compounds exhibit low toxicity for human epithelial cells and have potential as microbicides which might be used to provide protection against sexual transmission of HIV.
Dixon
Dabney W
DW
Department of Chemistry, Georgia State University, Box 4098, Atlanta, GA 30303, USA. ddixon@gsu.edu
Gill
Anila F
AF
Giribabu
Lingamallu
L
Vzorov
Andrei N
AN
Alam
Atia B
AB
Compans
Richard W
RW
D000476:Alkanesulfonates / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002614:Chelating Agents / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry; D019075:Electrophoresis, Capillary; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship; D013997:Time Factors
D000476:Alkanesulfonates; D019380:Anti-HIV Agents; D002614:Chelating Agents; D003505:Cyclodextrins; D011166:Porphyrins; D003300:Copper; D007501:Iron