5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies

Abstract

Background: Infectious diseases symbolize a global consequential strain on public health security and impact on the socio-economic stability all over the world. The increasing resistance to the current antimicrobial treatment has resulted in crucial need for the discovery and development of novel entity for the infectious treatment with different modes of action that could target both sensitive and resistant strains. Methods: Compounds were synthesized using classical methods of organic synthesis. Results: All 20 synthesized compounds showed antibacterial activity against eight Gram-positive and Gram-negative bacterial species. It should be mentioned that all compounds exhibited better antibacterial potency than ampicillin against all bacteria tested. Furthermore, 18 compounds appeared to be more potent than streptomycin against Staphylococcus aureus, Enterobacter cloacae, Pseudomonas aeruginosa, Listeria monocytogenes, and Escherichia coli. Three the most active compounds 4h, 5b, and 5g appeared to be more potent against MRSA than ampicillin, while streptomycin did not show any bactericidal activity. All three compounds displayed better activity also against resistant strains P. aeruginosa and E. coli than ampicillin. Furthermore, all compounds were able to inhibit biofilm formation 2-to 4-times more than both reference drugs. Compounds were evaluated also for their antifungal activity against eight species. The evaluation revealed that all compounds exhibited antifungal activity better than the reference drugs bifonazole and ketoconazole. Molecular docking studies on antibacterial and antifungal targets were performed in order to elucidate the mechanism of antibacterial activity of synthesized compounds. Conclusion: All tested compounds showed good antibacterial and antifungal activity better than that of reference drugs and three the most active compounds could consider as lead compounds for the development of new more potent agents.

3-Amino-5-(indol-3-yl)methylene-4-oxo-2-thioxothiazolidine Derivatives as Antimicrobial Agents: Synthesis, Computational and Biological Evaluation

“…It should be mentioned that the tested compounds interact more strongly with the heme group of the enzyme CYP51 Ca because the heme’s Fe is involved in this interaction. In the case of our previous work [ 19 ], the most active compound interacts with the heme but throughout its benzene ring and the –NO 2 group, forming pi and negative ionizable interactions with the heme group, respectively. In the case of 5-adamantane thiadiazole-based thiazolidinones [ 72 ] , again, the most active compound form positive interactions between the heme group and heterocyclic rings of the compound.…”

“…Therefore, the design and development of hybrid molecules combining thiazolidinone and indole cores in the same structure is a promising approach. Taking into account all issues mentioned above and encouraging results obtained in our earlier studies [ 19 ], in this paper, we present the synthesis and biological evaluation of new (1H-indole-3-yl-methylene)-4-oxo-2-thioxothiazolidin derivatives with potent antimicrobial activity.…”

“…The combination of the thiazolidinone ring with other pharmacologically promising heterocycles has been a warranted approach for developing new “drug-like” molecules with the desired activity profile [ 29 , 30 , 31 ]. Our previous studies showed that thiazolidinone core with indole fragment in one molecule gave the compounds with high antimicrobial activity [ 19 ].…”

Synthesis of indoline-thiazolidinone hybrids with antibacterial and antifungal activities

“…The starting rhodanine-3-propanoic/ethanesulfonic acids 1,2 were obtained according to the known synthetic methods [17,31]. Melting points were measured in open capillary tubes and were uncorrected.…”

“…Among the design strategies in drug discovery, considerable interest has been paid to thiazole-based heterocycles [3][4][5]. Thiazole/thiazolidinone derivatives constitute an important class of therapeutic agents in medicinal chemistry including antitrypanosomal [6], antiviral [7,8], anticancer [9][10][11], antioxidant [12,13], anti-inflammatory [14][15][16] activities and also display a pivotal role as antimicrobial and antifungal agents [17,18]. Thus, a thiazole ring is present in several drugs, such as penicillin, monobactam, sulfathiazole, thiabendazole and nizatidine, making this heterocyclic fragment ideal for construction more potent and safer drug candidates, especially in the therapy of infectious diseases (Fig.…”