Antimicrobial Activities of 3-Amino- and Polyaminosterol Analogues of Squalamine and Trodusquemine

Figures & data

Scheme 1 Structure of Squalamine 1 and Trodusquemine 2.

Scheme 2 Titanium(IV) Reductive Amination Reaction of 4-Cholesten-3 one 3 cholestan-3-one 5 and 5-Cholesten-3-one 7 using various amines ^aReactions performed at 20°C for 12 h in MeOH on a 0.78 mmol scale of ketone 5 or 7 in the presence of Ti(Oi-Pr)₄ (1.03 mmol) and the desired amine (2.34 mmol). ^bIsolated yields.

Table I.  Antimicrobial Activities of Aminosterol Derivatives 4, 6, 8.

	Antimicrobial activity (MIC), μM
Sample	S. cerevisiae	C. albicans	C. tropicalis	S. aureus	E. faecalis	E. hirae	E. coli
Streptomycin	–	–	–	25	–	25	25
Econazole	8.2	32	32	–	–	–	–
Squalamine	45	− 90	–	2	20	20	2
4b	25	25	12.5	3.12	50	6.25	>100
4c	>100	>100	50	25	>100	12.5	>100
4d	>100	50	>100	12.5	>100	12.5	>100
4e	25	6.25	6.25	6.25	6.25	6.25	>100
4f	>100	>100	–	50	6.25	6.25	>100
4g	>100	>100	>100	>100	>100	25	>100
4h	>100	>100	>100	>100	>100	12.5	>100
4i	>100	>100	25	>100	>100	3.12	>100
4j	>100	>100	6.25	>100	>100	12.5	>100
4k	>100	>100	12.5	>100	>100	12.5	>100
4l	>100	>100	12.5	>100	>100	12.5	>100
4m	>100	100	>100	6.25	>100	12.5	>100
4n	12.5	50	12.5	6.25	12.5	6.25	>100
4o	>100	>100	>100	50	>100	>100	>100
4p	100	50	>100	6.25	12.5	6.25	>100
4q	>100	>100	>100	>100	>100	12.5	>100
4r	6.25	50	>100	6.25	>100	12.5	>100
6a	>100	>100	−	>100	>100	25	>100
6b	25	25	50	12.5	−	6.25	>100
6c	100	>100	−	25	>100	25	>100
6d	>100	>100	>100	>100	>100	25	>100
6e	100	50	50	25	>100	12.5	>100
6f	50	100	25	12.5	100	25	>100
6g	>100	>100	>100	>100	>1000	25	>100
6h	>100	>100	>100	>100	>100	25	>100
6m	12.5	100	>100	6.25	25	3.12	>100
6p	25	50	>100	12.5	25	3.12	>100
6r	>100	>100	>100	>100	100	6.25	>100
8b	6.25	12.5	>100	50	12.5	6.25	>100
8c	50	>100	>100	25	50	50	25
8d	>100	>100	>100	12.5	12.5	12.5	25
8e	>100	>100	>100	6.25	12.5	6.25	25
8m	>100	>100	>100	>100	>100	25	>100
8n	12.5	>100	>100	>100	50	6.25	>100
8p	12.5	>100	>100	>100	25	6.25	>100
8r	>100	>100	>100	>100	12.5	6.25	>100