## 4 Antimicrobial Agents
### Secondary Metabolites  
Secondary metabolites (SM) do not directly contribute to the basal metabolism of its producing organism instead act as essential factors to either attract, repel, or kill other organisms and thereby increase the chance of self-survival [42; 95]. Unique secondary plant metabolites such as _Citrus limonoids_ presented their potential to affect biofilm formation and cell-cell signaling in _Vibrio harveyi_ by modulating the expression LuxO, but not the promoter activity of LuxR (Table 2) [42]. Since marine organisms are a rich source of novel bioactive metabolites, studies on marine fungal and bacterial secondary metabolites have been gradually growing for the development of novel therapeutic agents [96]. For example, a secondary metabolite identified as cyclo(l-Tyr-l-Leu) produced from a marine ascomycete _Penicillium_ spp isolated from the sponge _Axinella corrugata_ which inhibited biofilm formation by _S. epidermidis_[43]. Similarly, [PERSON] et al. described the discovery of three novel secondary peptitic metabolites known as cahuitamycins from _Streptomyces gandocaensis_ that were the inhibitors of _Acinetobacter baumanniii_ biofilms [44]. Thus, secondary metabolites could be abundantly found where the \begin{table}
\begin{tabular}{c c c c c c} \hline \hline  & **Small Organic Molecules** & **Biological Role** & **Effective Against** & **Type of Compound** & **Reference** \\ \hline
1 & 5-phenyl-2-aminoimidazole & Reduction in transription of CsgD, csgB and adrA & _S. typhimurium_ & Imidazole derivative & [79] \\ \hline
2 & ABC-1 & Reduction in SpA and PIA production and decrease eDNA release & _S. aureus_, Gram-positive and Gram-negative pathogens & Imidazole derivative & [1; 80] \\ \hline
3 &
\begin{tabular}{c} 5,6-dimethoxy-2-aminobenzimidazole \\ \end{tabular} & Reduction in QS receptors (LasR and RhIR) & _P. aeruginosa_ & Imidazole derivative & [81] \\ \hline
4 & Pyrazolo-pyrimidines [4,5-d] pyrimidines & ROS accumulation, loss of membrane integrity & _M. luteus, S. aureus_, _B. subtilis, E. coli_, _K. planticola_ & pyrazole compound & [82; 83; 84] \\ \hline
5 &
\begin{tabular}{c} Indole-3-carboxaldehyde and 3-indolylacetonitrile \\ \end{tabular} & Reduction of curli production & _E. coli, P. aeruginosa_ & indole and carbazole derivative & [85; 86] \\ \hline
6 & Phenylhydrazine analogues & StrA inhibition & _S. aureus_ &
\begin{tabular}{c} 2-Phenylhydrazineylidene \\ derivatives \\ \end{tabular} & [87] \\ \hline
7 &
\begin{tabular}{c} Diethyl 1-(2-chlorophenyl)- \\ 4-((3-chlorophenyl)amino)- \\ 5-oxo-2,5-dihydro-1H- \\ pyrrole-2,3-dicarboxylate \\ \end{tabular} & MDH and eDNA inhibition & _P. aeruginosa_ & Pyrrole derivatives & [90] \\ \hline
8 &
\begin{tabular}{c} (Z)-5-bromomethylhene- \\ 2(5H)-furan \\ \end{tabular} & AI-2-mediated QS inhibition & _S. anginosus_, _S.intermedius_ and _S. mutans_ & Furanone and _oxazolitionen derivatives_ & [91] \\ \hline
9 &
\begin{tabular}{c} Bicyclic brominated \\ furanones \\ \end{tabular} & AI-2-mediated QS inhibition & _F. nucleatum, P. gingrials_ and _T. forysthia_ & Furanone and _G_oxazolitionen derivatives & [91] \\ \hline
10 & Halogenated phenazine &
\begin{tabular}{c} Bind with copper (II ) \\ and iron (II) \\ \end{tabular} & MRSA, MMSE, and VRE & Phenazine and quinolone derivative & [92] \\ \hline
11 & Quinolone compound Ia & PqSR inhibition & _P. aeruginosa_ & Quinolone derivative & [93] \\ \hline
12 &
\begin{tabular}{c} 3,4-dimethoxyoxinamide \\ derivative \\ \end{tabular} & LecB inhibition & _P. aeruginosa_ & Cinnamide derivative of & [94] \\ \hline \hline \end{tabular}
\end{table} 
Table 4: Small organic molecules with the known biofilm inhibition or eradication mechanism. microorganisms coexist together. This highlights that nature could be an unlimited source for drug discovery. Seaweed secondary metabolites such as phlorotannin possess antibacterial properties. Several in vivo studies and clinical trials exist on the health benefits of Phlorotanin.