Antimicrobial Evaluation and Structure-Activity Relationship (SAR) of Some 1,ω-bis[4-Carboxy/Methoxycarbonyl/(Hydrazinecarbonyl)/Phenoxy]Alkanes

Abstract

A series of some 1,ω-bis[4-carboxy/methoxycarbonyl/(hydrazinecarbonyl)/phenoxy]alkanes were synthesized and evaluated for their antimicrobial activity against different strains of Gram-positive bacteria (Bacillus subtilis RCMB 101-001  and Staphylococcus aureus RCMB 106-001 (1)), Gram-negative bacteria (Pseudomonas aeruginosa RCMB 102-002 and Escherichia coli RCMB 103-001), yeast (Candida albicansRCMB 005003) and fungi (Aspergillus fumigates RCMB 002008 (1), Penicillium italicum RCMB 001018 (1) and Syncephalastrum racemosum RCMB 016001). The screening results revealed that all the tested compounds exhibited different inhibitory effects against different organisms. Thus, compounds 1, 4, exhibited inhibitory effects against all the test organisms, compounds 5, 7 exhibited inhibitory effects against seven of total eight test organisms, compound 2 exhibited inhibitory effect against six of total eight test organisms. Some tested compounds, at specific concentrations, showed the same or higher inhibitory effects against some test organisms, compared to standard antimicrobial agents, at the same concentrations. Thus, while compound 1 gave the same inhibitory effect against Aspergillus fumigatus RCMB 002008 (1) (at concentrations 1.0, 2.5 and 5.0 mg/mL) as Tebinafine (standard antifungal agent), it showed much higher inhibitory effect against Syncephalastrum racemosum RCMB 016001 (at concentrations 2.5 and 5.0 mg/mL) and Candida albicans RCMB 005003 (at concentrations 1, 2.5 and 5 mg/mL). Compound 7, also, compared to Terbinafine, while revealed the same inhibitory effect, against Penicillium italicum RCMB 001018 (1) (at concentrations 1.0, 2.5 and 5.0 mg/mL), it revealed higher inhibitory effect against Aspergillus fumigatus RCMB 002008 (1) (at concentration 5.0 mg/mL), Syncephalastrum racemosum RCMB 016001 (at concentration 2.5 mg/mL) and Candida albicans RCMB 005003 (at concentration 5.0 mg/mL). Compared to the standard antibacterial Chloramphenicol, compound 7 revealed the same inhibitory effect against Staphylococcus aureus RCMB 106-001 (1) (at concentrations 1.0, 2.5 and 5 mg/mL) and Escherichia coli RCMB 103-001 (at concentrations 1.0, 2.5 and 5 mg/mL).The structure-activity relationship was investigated via studying the effect of the aliphatic spacer length between the two ethereal oxygen atoms as well as the effect of functional group attached to the two carbonyl groups (hydroxy/methoxy/hydrazine) on the inhibitory effect of the titled compounds.