Steroid alkaloids and uses thereof as antimicrobial agents against electron transport-deficient microbes and as potentiators for antimicrobial agents against pathogenic bacteria

A method of preventing or treating an infection caused by a bacterial pathogen of the Firmicutes phylum in a subject, said method comprising administering to said subject a therapeutically effective amount of a compound or a composition comprising the compound and a pharmaceutically acceptable carrier, in combination with an aminoglycoside antibiotic, the compound being;

• (i) a compound of formula:
• wherein,
• (1) R1 is H, OH, NH2, NHR12, N(R12)(R12′), OR12 or SR12;
• and R2=H;
• or
• (2) R2 is H, OH, NH2, NHR12, N(R12)(R12′), OR12 or SR12;
• and R1=H;
• or
• (3) R1 and R2 together form ═O or ═NR12;
• R3 is α-H, β-H, α-alkyl, β-alkyl, α-OH or β-OH, or is absent when the double bond is present either in C4=C5, or in C5=C6;
• - - - - - is an optional double bond;
• R4-R6 are identical or different and are H, alkyl, OH, OR18, NHR18 or N(R18)(R18′);
• R7 is H, α-OH or β-OH;
• R8 is α-H, α-OH or β-OH;
• X and Y are identical or different and are O, NR19, or CH2;
• R12 and R12′ are identical or different and are H, alkyl, aryl, COalkyl, COaryl, CO2alkyl, CO2aryl, CONHalkyl, CONHaryl, SO3H, SO2alkyl, SO2aryl, SO2N(R14)p, PO3H2, CO—CH(R20)NH2, (CH2)n′—NH—R14, C(═NH)NHR21, CH3OCH2, Silylalkyl, (CH2)mCO2H, (CH2)mSO3H, (CH2)mNH2, (CH2)mNHC(═NH)NH2, (CH2)m—C(═NH)NH2, NHalkyl or NHaryl;
• R14, R22 and R22′ are identical or different and are H, alkyl, aryl, COalkyl, CO2alkyl, COaryl, CO2aryl, SO2alkyl, SO2aryl, SO2N(alkyl)p′ or CO—CH(R20)NH2;
• R18 and R18′ are identical or different and are H, alkyl, aryl, COalkyl, COaryl, CONHalkyl, CONHaryl, SO3H, SO2alkyl, SO2aryl, SO2N(alkyl)p″, PO3H2, CO—CH(R20′)NH2, (CH2)n″—NH—R22, C(═NH)NHR21′, (CH2)m′CO2H, (CH2)m′SO3H, (CH2)m′NH2, (CH2)m′NHC(═NH)NH2, (CH2)m′—C(═NH)NH2, NHalkyl or NHaryl;
• R19 is H, alkyl, aryl, COH, COalkyl, COaryl, CO2alkyl, CO2aryl, CONHalkyl, CONHaryl, SO3H, SO2alkyl, SO2aryl, SO2N(Ralkyl)p′″, PO3H2, CO—CH(R20″)NH2, (CH2)n′″—NH—R22′, C(═NH)NHR21″, (CH2)m″CO2H, (CH2)m″SO3H, (CH2)m″NH2, (CH2)m″NHC(═NH)NH2, (CH2)m″—C(═NH)NH2, NHalkyl or NHaryl;
• R20, R20′ and R20″ are identical or different and correspond to the side chain of any L- and D- amino acid;
• R21, R21′ and R21″ are identical or different and are H, alkyl, OH, Oalkyl, Oaryl, NHalkyl, NHaryl, N(alkyl)2, N(aryl)2, or N(alkyl)(aryl);
• n, n′, n″ and n′ are identical or different and are 0-5;
• m, m′ and m″ are identical or different and are 1-5;
• and
• p, p′, p″ and p′″ are identical or different and are 1-2;
• or a salt, stereoisomer or any mixture of stereoisomers of the compound of formula 1.0,
• whereby said bacterial infection is prevented or treated.