ABSTRACT
In this paper, we have reported seventeen novel synthetic organic compounds derived from marine bromopyrrole alkaloids, exhibiting potential inhibition of biofilm produced by Gram-positive bacteria. Compound 5f with minimumbiofilm inhibitory concentration(MBIC) of 0.39, 0.78 and 3.125 µg/mL against MSSA, MRSA and SE respectively, emerged as promising anti-biofilm lead compounds. In addition, compounds 5b, 5c, 5d, 5e, 5f, 5h, 5i and 5j revealed equal potency as that of the standard drug Vancomycin (MBIC = 3.125 µg/mL) against Streptococcus epidermidis. Notably, most of the synthesized compounds displayed better potency than Vancomycin indicating their potential as inhibitors of bacterial biofilm. The cell viability assay for the most active hybrid confirms its anti-virulence properties which need to be further researched.
Subject(s)
Alkaloids/chemistry , Anti-Bacterial Agents/chemical synthesis , Gram-Positive Bacteria/physiology , Alkaloids/chemical synthesis , Alkaloids/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Aquatic Organisms/chemistry , Aquatic Organisms/metabolism , Biofilms/drug effects , Cell Survival/drug effects , Chlorocebus aethiops , Gram-Positive Bacteria/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Quorum Sensing/drug effects , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Streptococcus/drug effects , Structure-Activity Relationship , Vero CellsABSTRACT
We report synthesis and antimicrobial evaluation of 42 novel 4-nitropyrrole-based 1,3,4-oxadiazoles. The synthesized molecules were evaluated for anti-bacterial, anti-fungal and anti-tubercular activities. Promisingly, most of the compounds showed equal or more potency than standard ciprofloxacin against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. Compound 5e exhibited highest anti-tubercular activity (0.46 µg/mL) close to that of standard Isoniazid (0.40 µg/mL). Equal antifungal activity (1.56 µg/mL) compared to standard Amphotericin-B was shown by most of the compounds. All the N-methylated compounds showed more potent to equal activity against MSSA (MIC 0.39-1.56 µg/mL) and MRSA (MIC 0.78-1.56 µg/mL). All compounds were tested for mammalian cell toxicity using VERO cell line and were found to be non-toxic.
Subject(s)
Antibiotics, Antitubercular/pharmacology , Antifungal Agents/pharmacology , Oxadiazoles/pharmacology , Pyrroles/chemistry , Animals , Antibiotics, Antitubercular/chemical synthesis , Antibiotics, Antitubercular/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Bacillus subtilis/drug effects , Candida albicans/drug effects , Chlorocebus aethiops , Dose-Response Relationship, Drug , Escherichia coli/drug effects , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium tuberculosis/drug effects , Oxadiazoles/chemical synthesis , Oxadiazoles/chemistry , Staphylococcus aureus/drug effects , Structure-Activity Relationship , Vero CellsABSTRACT
A series of twenty three novel hybrids of marine bromopyrrole alkaloids with chalcone, isoxazole and flavone structural features were synthesized and evaluated for in vitro anticancer activity by MTT assay against five human cancer cell lines. Among the synthesized chalcones, hybrids 4a and 4h (IC50 range: 0.18 µM-12.00 µM) showed anticancer activity against all the tested cancer cell lines. Promising cytotoxic activities were exhibited by flavones derivatives, 5a and 5b (0.41 µM-1.28 µM) against cell lines PA1 and KB403. Isoxazole hybrids, 6b-6e selectively inhibited oral and mouth cancer cell line KB403, among which 6c (IC50 = 2.45 µM) was found to be most active.
