Feature-Based Molecular Networking Discovery of Bromopyrrole Alkaloids from the Marine Sponge <i>Agelas dispar</i>.
Freire VF, Gubiani JR, Spencer TM, Hajdu E, Ferreira AG, Ferreira DAS, de Castro Levatti EV, Burdette JE, Camargo CH, Tempone AG, Berlinck RGS.
Investigation of the marine sponge <i>Agelas dispar</i> MeOH fractions using feature-based molecular networking, dereplication, and isolation led to the discovery of new bromopyrrole-derived metabolites. An in-house library of bromopyrrole alkaloids previously isolated from <i>A. dispar</i> and <i>Dictyonella</i> sp. was utilized, along with the investigation of an MS/MS fragmentation of these compounds. Our strategy led to the isolation and identification of the disparamides A-C (<b>1</b>-<b>3</b>), with a novel carbon skeleton. Additionally, new dispyrins B-F (<b>4</b>-<b>8</b>) and nagelamides H2 and H3 (<b>9</b> and <b>10</b>) and known nagelamide H (<b>11</b>), citrinamine B (<b>12</b>), ageliferin (<b>13</b>), bromoageliferin (<b>14</b>), and dibromoageliferin (<b>15</b>) were also isolated and identified by analysis of spectroscopic data. Analysis of MS/MS fragmentation data and molecular networking analysis indicated the presence of hymenidin (<b>16</b>), oroidin (<b>17</b>), dispacamide (<b>18</b>), monobromodispacamide (<b>19</b>), keramadine (<b>20</b>), longamide B (<b>21</b>), methyl ester of longamide B (<b>22</b>), hanishin (<b>23</b>), methyl ester of 3-debromolongamide B (<b>24</b>), and 3-debromohanishin (<b>25</b>). Antibacterial activity of ageliferin (<b>13</b>), bromoageliferin (<b>14</b>), and dibromoageliferin (<b>15</b>) was evaluated against susceptible and multi-drug-resistant ESKAPE pathogenic bacteria <i>Klabsiella pneumoniae</i>, <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, <i>Pseudomonas aeruginosa</i>, <i>Acinetobacter baumannii</i>, and <i>Enterococcus faecalis</i>. Dibromoageliferin (<b>15</b>) displayed the most potent antimicrobial activity against all tested susceptible and MDR strains. Compounds <b>13</b>-<b>15</b> presented no significant hemolytic activity up to 100 μM.