The burden of antibiotic resistance necessitates a continued search for new antimicrobials. We evaluated the antimicrobial activities of novel benzothiazoles synthesized by our group. Antibacterial activity was evaluated in vitro in Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, while the antifungal activity was tested in Candida albicans and Aspergillus niger, and expressed as the minimum inhibitory concentration (MIC; µg/mL). MIC values of benzothiazole compounds ranged from 25 to 200 µg/mL. Compounds 3 and 4 gave high antibacterial and moderate antifungal activities, while 10 and 12 showed moderate activity against all tested organisms. In addition, some benzothiazole compounds significantly suppressed the activity of Escherichia coli dihydroorotase and inhibited the dimorphic transition of Candida albicans. Moreover, the active benzothiazole compounds induced DNA and protein leakage in Aspergillus niger spores. Molecular interactions of benzothiazole derivatives with dihydroorotase revealed the formation of hydrogen bonds with the active site residues LEU222 or ASN44. Strong hydrophobic interactions of the bulky thiazole and naphthalene rings at the entrance to the active site might interfere with the access of substrates to their binding sites, which results in dihydroorotase inhibition. Thus, inhibition of dihydroorotase might contribute to the observed antimicrobial actions of these compounds.

The approaches used for the green biosynthesis of nanoparticles with clinical applications have been widely used in nanotechnology due to their potential to provide safe, eco-friendly, cost effective, high-stability, and high-loading-capacity nanoparticles. This study aimed to evaluate the anti-candidal activity of silver nanoparticles (AgNPs) biosynthesized using the aqueous leaf extract of Calotropis gigantea (CG) alone or in a combination with the plant extract of CG (AgNPs/CG). AgNPs were characterized using UV-Vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The results of the standard disk diffusion method revealed that AgNPs alone displayed anti-candidal activity (11.33-mm inhibition zone), while AgNPs/CG displayed a strong synergistic anti-candidal activity (17.76-mm inhibition zone). Similarly, AgNPs/CG completely inhibited the growth of C. albicans after 4 h of incubation, as measured using the time-kill assay. In addition, AgNPs/CG inhibited the dimorphic transition of C. albicans and suppressed both the adhesion and the biofilm formation of C. albicans by 41% and 38%, respectively. The treatment of Candida. albicans with AgNPs/CG showed a significant inhibition of the production of several antioxidant enzymes. Interestingly, AgNPs/CG did not show any cytotoxicity in animal cells, including the MCF-7 cell line and primary mouse bone marrow-derived mesenchymal stem cells (mBMSCs), at the concentration used to completely inhibit the dimorphic transition of C. albicans. In conclusion, we identified AgNPs/CG as a promising natural-product-based nanoparticle that can potentially be used as an anti-candidal drug.

Oral candidiasis is widely spread in both humans and animals, which is caused mainly by Candida albicans. In this study, we aimed to biosynthesize silver nanoparticles (AgNPs) for the first time using the Lotus lalambensis Schweinf leaf extract (L-AgNPs) and investigated their anti-candidal potency alone or in combination with the leaf extract of L. lalambensis (L-AgNPs/LL) against C. albicans. The biosynthesized L-AgNPs were characterized by imaging (transmission electron microscopy, TEM), UV−vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The results of the disk diffusion method showed the potent synergistic anti-candidal activity of L-AgNPs/ LL (24 mm inhibition zone). L-AgNPs/LL completely inhibited the morphogenesis of C. albicans and suppressed the adhesion and the formation of the biofilm of C. albicans by 82.5 and 78.7%, respectively. Further, L-AgNPs/LL inhibited the production of antioxidant enzymes of C. albicans by 80%. SEM and TEM revealed deteriorations in the cell wall ultrastructure in L-AgNPs/LL-treated C. albicans. Interestingly, L-AgNPs/LL showed less than 5% cytotoxicity when examined with either the primary bone marrow derived mesenchymal stem cell (BMSCs) or MCF-7 cell line at MIC values of L-AgNPs/LL. In conclusion, we identified L-AgNPs/LL as a potential biosynthesized-based drug for oral candidiasis in humans and animals.