# Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance
## 5 Emerging Antibiofilm Agents
### Natural Compounds  
[PERSON] et al. evaluated resveratrol as a biofilm inhibitor against _Aeromonas hydrophila_. The significant reduction in biofilm formation using resveratrol (**25**) was noted at concentrations higher than 0.25 ug/mL and a 49.11% reduction in biofilm biogenesis was observed with 4 ug/mL [196]. [PERSON] et al. investigated Raffinose (**26**), which is a \(\alpha\)-galactosyl derivatives of sucrose, and their isolate from finger extract and evaluated for their ability to prevent biofouling in membrane bioreactors involved in membrane filtration and treatment of waste water. It was observed that the extract significantly reduced 25-52% of the _P. aeruginosa_ and _S. aureus_ co-culture biofilms at a concentration range of 0-1000 uM. In addition, Raffinose also decreased the transmembrane pressure in lab-scale membrane bioreactors compared to furanone C-30 used as control [197]. In a study by [PERSON] et al., Pseudomonas species producing metallo-b-lactamase (MbLs) enzymes from camel meat were isolated and evaluated for their ability to form biofilms. Additionally, the effect of the flavone naringin (**27**) on the biogenesis of biofilm against the isolated Pseudomonas species was assessed by in silico and in vitro studies. A total of 55% isolates were found to produce MbLs. Naringin attenuated up to 57% of the biofilm formation in the isolated Pseudomonas species. Naringin remarkably turned down biofilms EPS and alginate density. Disruption of preformed biofilms from 32-60% was seen at respective 0.50 MICs. Naringin can thus be explored as a promising food preservative against foodborne Pseudomonas species forming biofilms [198]. In recent work by [PERSON] et al. the biofilm inhibition ability of unsolic acid (**28**) was evaluated towards oral Streptococcus species. Ursolic acid being a natural product can be derived from plant parts such as privet leaves, berries, loquat leaf, paulownia leaves and  
Figure 11: Chemical structures of some quaternary ammonium compounds. iron holly. It was observed that unsolic acid inhibits multi-species biofilms of _S. mutans_, _S. gordonii_ and _S. sanguinis_ at a concentration of 7.80 \(\mathrm{\SIUnitSymbolMicro mL}\). Moreover they inhibited specifically glucosyltransferases the prime cariogenic component of oral biofilms and displayed relatively less cytotoxicity towards human oral cells [199]. [PERSON] et al. and [PERSON] et al. recently investigated the outcome of phloretin (**29**) on _Listeria monocytogenes_ biofilm formation. Phloretin in sub-MIC levels was used at different temperatures of 37 \({}^{\circ}\)C and 4 \({}^{\circ}\)C to treat the biofilm. It showed maximum inhibition of the biofilm up to 60% with a concentration of 20 \(\mathrm{\SIUnitSymbolMicro mL}\). Moreover, the amount of biofilm aggregation and adhesion in _L. monocytogenes_ was subsequently diminished. The thickness of the biofilm was lessened by 2 \(\mathrm{\SIUnitSymbolMicro m}\) at a concentration of 20 \(\mathrm{\SIUnitSymbolMicro mL}\). The mode of biofilm inhibition study revealed the role of phloretin reducing the QS related gene _agr_ by 50% with 20 \(\mathrm{\SIUnitSymbolMicro mL}\) phloretin [200; 201]. [PERSON] et al. investigated Baicalin (**30**), a natural compound derived from the roots of _Scutellaria bacialensis_, and evaluated its ability to inhibit biofilm formation in _Staphylococcus saprophyticus_ and its QS by selectively inhibiting the MsrA drug efflux pump. The study displayed promising results with baicalin decreasing biofilm biogenesis, and bacterial aggregation by downstreaming the mRNA transcription proportion of the QS regulators agrA, agrC, sarA and RNAIII [202; 203]. [PERSON] et al. evaluated three flavonoids from _Brosimum acutiifolium_, 4'-hydroxy-7,8(2'',2''-dimethylpyran) flavan (**31**), brosimine b (**32**) and 4-hydroxy-lonchocarpin (**33**), as antibiofilm agents. A and B decreased the viability in preformed _S. aureus_ biofilms upto 73% at a concentration of 50 \(\mathrm{\SIUnitSymbolMicro m}\).