Gold(I) analogues of a platinum-acridine antitumor agent are only moderately cytotoxic but show potent activity against Mycobacterium tuberculosis.
Cationic gold(I) complexes containing 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea (1), [AuL(1)](n+) (where L is Cl(-), Br(-), SCN(-), PEt(3), PPh(3), or 1), derived from a class of analogous platinum(II) antitumor agents, have been synthesized. Unlike platinum, gold does not form permanent adducts with DNA, and its complexes are 2 orders of magnitude less cytotoxic in non-small-cell lung cancer cells than the most active platinum-based agent. Instead, several gold analogues show submicromolar and selective antimicrobial activity against Mycobacterium tuberculosis.
Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109, USA.
Lauren C
LC
Eiter
Nathan W
NW
Hall
Cynthia S
CS
Day
Gilda
G
Saluta
Gregory L
GL
Kucera
Ulrich
U
Bierbach
D000166:Acridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001682:Biological Availability; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002614:Chelating Agents / Q000138:chemical synthesis; D002522:Chlorocebus aethiops; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D018736:DNA Adducts / Q000096:biosynthesis; D004269:DNA, Bacterial / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006046:Gold; D006801:Humans; D008024:Ligands; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D050607:Organogold Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010984:Platinum; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D014709:Vero Cells
C471910:1-(2-(acridin-9-ylamino)ethyl)-1,3-dimethylthiourea; D000166:Acridines; D000970:Antineoplastic Agents; D000995:Antitubercular Agents; D002614:Chelating Agents; D056831:Coordination Complexes; D018736:DNA Adducts; D004269:DNA, Bacterial; D008024:Ligands; D050607:Organogold Compounds; D010984:Platinum; D006046:Gold; D014508:Urea; D013890:Thiourea