TY - JOUR
T1 - Molecular networking reveals two distinct chemotypes in pyrroloiminoquinone-producing tsitsikamma favus sponges
AU - Kalinski, Jarmo Charles J.
AU - Waterworth, Samantha C.
AU - Noundou, Xavier Siwe
AU - Jiwaji, Meesbah
AU - Parker-Nance, Shirley
AU - Krause, Rui W.M.
AU - McPhail, Kerry L.
AU - Dorrington, Rosemary A.
N1 - Funding Information:
This research was funded by grants to R.A.D. from the South Africa Research Chair Initiative (SARChI) grant from the South African National Research Foundation (NRF) (GUN: 87583), the NRF African Coelacanth Ecosystem Programme (GUN: 97967); the NRF Communities of Practice Programme (GUN: 110612) and a Self-Initiated Research grant (2018-2021) from the South African Medical Research Council. J.-C.J.K. was supported by NRF SARChI MSc and PhD Fellowships, S.C.W. was supported by an NRF Innovation PhD Scholarship and a Rhodes University Henderson Scholarship, M.J. was supported by an NRF Emerging Researcher Fellowship (GUN: 91468) and X.S.N. was the recipient of a Post-Doctoral Fellowship from Rhodes University. Opinions expressed and conclusions arrived at are those of the authors and are not attributed to any of the above-mentioned donors.
Funding Information:
Funding: This research was funded by grants to R.A.D. from the South Africa Research Chair Initiative (SARChI) grant from the South African National Research Foundation (NRF) (GUN: 87583), the NRF African Coelacanth Ecosystem Programme (GUN: 97967); the NRF Communities of Practice Programme (GUN: 110612) and a Self-Initiated Research grant (2018-2021) from the South African Medical Research Council. J.-C.J.K. was supported by NRF SARChI MSc and PhD Fellowships, S.C.W. was supported by an NRF Innovation PhD Scholarship and a Rhodes University Henderson Scholarship, M.J. was supported by an NRF Emerging Researcher Fellowship (GUN: 91468) and X.S.N. was the recipient of a Post-Doctoral Fellowship from Rhodes University. Opinions expressed and conclusions arrived at are those of the authors and are not attributed to any of the above-mentioned donors.
Publisher Copyright:
© 2019 by the authors.
PY - 2019/1/16
Y1 - 2019/1/16
N2 - The temperate marine sponge, Tsitsikamma favus, produces pyrroloiminoquinone alkaloids with potential as anticancer drug leads. We profiled the secondary metabolite reservoir of T. favus sponges using HR-ESI-LC-MS/MS-based molecular networking analysis followed by preparative purification efforts to map the diversity of new and known pyrroloiminoquinones and related compounds in extracts of seven specimens. Molecular taxonomic identification confirmed all sponges as T. favus and five specimens (chemotype I) were found to produce mainly discorhabdins and tsitsikammamines. Remarkably, however, two specimens (chemotype II) exhibited distinct morphological and chemical characteristics: the absence of discorhabdins, only trace levels of tsitsikammamines and, instead, an abundance of unbranched and halogenated makaluvamines. Targeted chromatographic isolation provided the new makaluvamine Q, the known makaluvamines A and I, tsitsikammamine B, 14-bromo-7,8-dehydro-3-dihydro-discorhabdin C, and the related pyrrolo-ortho-quinones makaluvamine O and makaluvone. Purified compounds displayed different activity profiles in assays for topoisomerase I inhibition, DNA intercalation and antimetabolic activity against human cell lines. This is the first report of makaluvamines from a Tsitsikamma sponge species, and the first description of distinct chemotypes within a species of the Latrunculiidae family. This study sheds new light on the putative pyrroloiminoquinone biosynthetic pathway of latrunculid sponges.
AB - The temperate marine sponge, Tsitsikamma favus, produces pyrroloiminoquinone alkaloids with potential as anticancer drug leads. We profiled the secondary metabolite reservoir of T. favus sponges using HR-ESI-LC-MS/MS-based molecular networking analysis followed by preparative purification efforts to map the diversity of new and known pyrroloiminoquinones and related compounds in extracts of seven specimens. Molecular taxonomic identification confirmed all sponges as T. favus and five specimens (chemotype I) were found to produce mainly discorhabdins and tsitsikammamines. Remarkably, however, two specimens (chemotype II) exhibited distinct morphological and chemical characteristics: the absence of discorhabdins, only trace levels of tsitsikammamines and, instead, an abundance of unbranched and halogenated makaluvamines. Targeted chromatographic isolation provided the new makaluvamine Q, the known makaluvamines A and I, tsitsikammamine B, 14-bromo-7,8-dehydro-3-dihydro-discorhabdin C, and the related pyrrolo-ortho-quinones makaluvamine O and makaluvone. Purified compounds displayed different activity profiles in assays for topoisomerase I inhibition, DNA intercalation and antimetabolic activity against human cell lines. This is the first report of makaluvamines from a Tsitsikamma sponge species, and the first description of distinct chemotypes within a species of the Latrunculiidae family. This study sheds new light on the putative pyrroloiminoquinone biosynthetic pathway of latrunculid sponges.
KW - Damirone
KW - Discorhabdin
KW - GNPS
KW - HR-ESI-LC-MS/MS
KW - Latrunculiidae
KW - Makaluvamine Q
KW - Pyrrolo-ortho-quinone
KW - Pyrroloquinoline
KW - Tsitsikammamine
UR - http://www.scopus.com/inward/record.url?scp=85060123832&partnerID=8YFLogxK
U2 - 10.3390/md17010060
DO - 10.3390/md17010060
M3 - Article
C2 - 30654589
AN - SCOPUS:85060123832
SN - 1660-3397
VL - 17
JO - Marine Drugs
JF - Marine Drugs
IS - 1
M1 - 60
ER -