Fungal biofilm inhibition by piperazine‐sulphonamide linked Schiff bases: Design, synthesis, and biological evaluation

Abstract

We report the synthesis of some new piperazine-sulphonamide linked Schiff bases as fungal biofilm inhibitors with antibacterial and antifungal potential. The biofilm inhibition result of Candida albicans proposed that the compounds 6b (IC = 32.1 μM) and 6j (IC = 31.4 μM) showed higher inhibitory activity than the standard fluconazole (IC = 40 μM). Compound 6d (MIC = 26.1 μg/mL) with a chloro group at the para position was found to be the most active antibacterial agent of the series against Bacillus subtilis when compared with the standard ciprofloxacin (MIC = 50 μg/mL). Compound 6j (MIC = 39.6 μg/mL) with an OH group at the ortho position showed more potent antifungal activity as compared to that of the standard fluconazole (IC = 50 μM) against C. albicans. Thus, the synthesized compounds 6a-k were found to be potent biofilm inhibitors as well as active antibacterial and antifungal agents. The molecular docking study of the synthesized compounds against the secreted aspartyl protease (SAP5) enzyme of C. albicans exhibited good binding properties. The in silico ADME properties of the synthesized compounds were also analyzed and showed their potential to be developed as potential oral drug candidates.

Rapid tools to gain insights into the interaction dynamics of new 8‐hydroxyquinolines with few fungal lines

“…In the late 1960s, there was a dramatic increase in fungal infections because of the development of antibiotic therapies (Vandeputte, Ferrari, & Coste, 2012), which represents a serious problem today. However, the number of antimicrobial medicines is limited, and it does not satisfy | 1187 JOAQUIM et Al. the need due to limitations related to the spectrum of action, potency, pharmacokinetic properties, and the emergent resistance of fungi and bacteria (Hipólito et al, 2018;Nett & Andes, 2016;Patil et al, 2018;Tobudic, Kratzer, & Presterl, 2012). In this context, the search and development of new antimicrobial therapies is imperative.…”

Tailoring of novel morpholine-sulphonamide linked thiazole moieties as dual targeting DHFR/DNA gyrase inhibitors: synthesis, antimicrobial and antibiofilm activities, and DFT with molecular modelling studies

“…The antimicrobial activity of the synthesized molecules 2-7 was assessed by conducting experiments on Muller Hinton agar (MHA) for bacteria and potato dextrose agar (PDA) for yeast. 3,4,8,10,21 An overnight culture of bacterial clinical isolates and Candida albicans ATCC10231 (standard strain) with a 0.5 McFarland standard was spread on the surface of MHA and PDA, respectively. Wells measuring 6 mm in diameter were created using a sterile cork borer, and then 100 mL of each compound was added to the wells.…”

“…5,8,9 Biochemically speaking, arylsulfonamides are a diverse group of favored organic sulfur motifs that have captured the attention of the pharmaceutical community as both market medications and prospective therapeutic opportunities. They are essential pharmacophores that are utilized as chemotherapeutic agents against a variety of illnesses with various biological actions such as antimicrobial, 10 antiglaucoma, 11 anticancer, 12 anticonvulsant, 13 and anti-inflammatory. 14 Sulfonamides became the first effective antibacterial drugs, paving the way for the antibiotic revolution in medical treatment.…”

“…They are broad-spectrum antibiotics that are effective against a wide range of bacterial strains, including Grampositive and Gram-negative, as well as some fungal and protozoal infections. 10,15 Sulfonamides are bacteriostatic, which means they do not kill bacteria but inhibit their capacity to grow and increase by inhibiting the bacterial biosynthesis of folic acid. 15 Sulfanilamide, sulfadiazine (SDZ), sulfadimethoxine, sulfamethoxazole, sulfamethazine (SMZ), sulfamerazine, sulfafurazole, sulfasalazine, and sulfisoxazole are examples of sulfonamide-derived antibiotics.…”

Exploring Anticandidal and Antibiofilm Potentials of Synthesized N-(Substitutedbenzylidene)-4,6-Dimethoxypyrimidin-2-Amine Analogues

“…Various synthetic routes were reported for the synthesis of diverse therapeutically active schiff bases such as pyrimidine schiff base, 20 piperazine schiff bases for their antifungal and antibacterial activity, sulphonamide schiff bases for antibacterial and antifungal activity, 21 piperazine, 22 piperazine, and sulphonamide coupled schiff bases for antimicrobial activities. 23 On the other hand, pyrimidine nitrogen-containing heterocyclic compounds are of great significance as they are abundant in nature and a wide spectrum of biological activities exhibited by the synthetic/semisynthetic derivatives. 24,25 Pyrimidine derivatives have shown a wide spectrum of biological activities such as antifungal (f-h), [24][25][26][27] antibiofilm (f-h), 25,26 antibacterial (a-e), 27 antiviral (j-k) 28 and anticancer (l-m).…”