- Marine Sponges and Natural Products
- Synthetic Organic Chemistry Methods
- Microbial Natural Products and Biosynthesis
- Bioactive Compounds and Antitumor Agents
- Cancer Treatment and Pharmacology
- Skin Protection and Aging
- Immunotherapy and Immune Responses
- Cell death mechanisms and regulation
- Immune Cell Function and Interaction
- Synthesis and Biological Activity
- ATP Synthase and ATPases Research
- Marine and coastal ecosystems
- Autophagy in Disease and Therapy
- Marine Toxins and Detection Methods
- Infectious Diseases and Mycology
- Aquatic Ecosystems and Phytoplankton Dynamics
- Urticaria and Related Conditions
- melanin and skin pigmentation
- 14-3-3 protein interactions
- Asymmetric Synthesis and Catalysis
- Cancer-related Molecular Pathways
- Beetle Biology and Toxicology Studies
- Phytochemical compounds biological activities
- Microtubule and mitosis dynamics
- Quinazolinone synthesis and applications
Harbor Branch Oceanographic Institute
2012-2023
Florida Atlantic University
2012-2023
University of Cambridge
2010
University of California, Riverside
2003-2009
Henry Ford Health System
2009
Sanford Burnham Prebys Medical Discovery Institute
2009
Henry Ford Hospital
2007
University of Houston
2007
The University of Texas MD Anderson Cancer Center
2006
The University of Texas Health Science Center at Houston
2003-2005
A new marine-derived macrolide designated as neopeltolide (1) has been isolated from a deep-water sponge of the family Neopeltidae. Its structure was elucidated on basis spectroscopic data interpretation. Neopeltolide is potent inhibitor in vitro proliferation A-549 human lung adenocarcinoma, NCI-ADR-RES ovarian sarcoma, and P388 murine leukemia cell lines, with IC50's 1.2, 5.1, 0.56 nM, respectively. also inhibited growth fungal pathogen Candida albicans minimum inhibitory concentration...
From the deep: Leiodermatolide is a structurally unique macrolide isolated from deep-water marine sponge Leiodermatium sp. which exhibits potent antiproliferative activity against range of human cancer cell lines and drastic effects on spindle formation in mitotic cells. Its unprecedented polyketide skeleton stereochemistry were established using combination experimental computational NMR methods. Detailed facts importance to specialist readers are published as "Supporting Information". Such...
Manzamine A, a member of the manzamine alkaloids, was originally isolated from marine sponges genus Haliclona. It recently shown to have activity against pancreatic cancer cells, but precise mechanism action remained unclear. To further our understanding chemogenomic profiling in yeast S. cerevisiae performed, suggesting that A is an uncoupler vacuolar ATPases. Fluorescence microscopy confirmed this effect on vacuoles, where produced phenotype very similar established v-ATPase inhibitor...
Abstract Background Metalloproteinase inhibitors can protect mice against experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Matrix metalloproteinase-9 (MMP-9) has been implicated, but it is not clear if other MMPs are also involved, including matrilysin/MMP-7 – enzyme capable of cleaving proteins that essential blood brain barrier integrity and immune suppression. Results Here we report MMP-7-deficient ( mmp7 -/- ) on the C57Bl/6 background...
Pancreatic cancer is the fourth leading cause of death in United States. The prognosis disease very negative, because will be usually metastasized by time a patient manifests symptoms. Although combination therapy shows some promise, new drugs to treat are needed. Given our interest finding therapies for pancreatic cancer, we sought determine whether known cytotoxic activity batzellines extended cell lines. pyrroloiminoquinones alkaloids obtained from deep-water Caribbean sponge Batzella sp...
A deep-water sponge of the genus Spongosorites has yielded a bis-indole alkaloid which we have named dragmacidin G. Dragmacidin G was first reported by us in patent literature and recently been Hitora et al. from Lipastrotheya. is this series compounds to pyrazine ring linking two indole rings. It also rare N-(2-mercaptoethyl)-guanidine side chain. shows broad spectrum biological activity including inhibition methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis, Plasmodium...
Pancreatic cancer, the fourth leading cause of cancer death in United States, has a negative prognosis because metastasis occurs before symptoms manifest. Leiodermatolide, polyketide macrolide with antimitotic activity isolated from deep water sponge genus Leiodermatium, exhibits potent and selective cytotoxicity toward pancreatic cell lines AsPC-1, PANC-1, BxPC-3, MIA PaCa-2, against skin, breast colon lines. Induction apoptosis by leiodermatolide was confirmed BxPC-3 PaCa-2 cells....
A hybrid library of the marine natural products dictyostatin and discodermolide, incorporating taxol or taxotere side chains, were synthesised; preliminary biological evaluation in PANC-1 cancer cell line revealed significant antiproliferative activity, demonstrating that a macrolide scaffold is an effective surrogate for baccatin core taxol.
Summary Microphthalmia ‐ associated transcription factor (Mitf) is essential for melanocyte development and function regulates anti‐apoptotic Bcl2 expression. We hypothesized that cellular deficiency of Mitf can influence survival in response to ultraviolet (UV) radiation. Primary cultures were prepared from neonatal wild‐type mice congenic animals heterozygous mutations mi‐vga9/+ Mi‐wh/+ exposed UV irradiation. Wild‐type melanocytes more resistant UV‐induced apoptosis than partially...
Abstract The design, synthesis, and biological evaluation of a series hybrids analogues the microtubule‐stabilizing anticancer agents dictyostatin, discodermolide, taxol is described. A 22‐membered macrolide scaffold was prepared by adapting earlier synthetic routes directed towards dictyostatin taking advantage distinctive structural stereochemical similarities between these two polyketide‐derived marine natural products. Initial endeavors accessing novel discodermolide/dictyostatin led to...
Background/purpose: Ultraviolet (UV) radiation is an important therapy for immune‐mediated cutaneous diseases. Activation of early apoptotic pathways may play a role in the clinical effectiveness. Different UV wavelengths have different efficacy various diseases, but it remains unclear whether ability to induce apoptosis differs with respect wavelength, and they through same mechanism. The aim this study analyze effects that are used clinically on normal human peripheral blood mononuclear...
A new adenine-substituted bromotyrosine-derived metabolite designated as aphrocallistin (1) has been isolated from the deep-water Hexactinellida sponge Aphrocallistes beatrix. Its structure was elucidated on basis of spectral data and confirmed through a convergent, modular total synthetic route that is amenable toward future analogue preparation. Aphrocallistin inhibits growth panel human tumor cell lines with IC50 values ranging 7.5 to >100 μM shown induce G1 cycle arrest in PANC-1...
Lasonolide A, a novel polyketide-derived macrolide, was previously identified from an extract of the marine sponge <i>Forcepia</i> sp. in assay for protein kinase C (PKC) inhibitors. Cytotoxicity testing and profiling lasonolide A National Cancer Institute (NCI) 60 cell panel screen revealed that it potent toward broad range lines also suggested unique mechanism action. Contrary to expected results, we found be strong activator PKC Panc-1 pancreatic carcinoma cells. Downstream...
Aus der Tiefe: Leiodermatolid, ein Makrolid mit einzigartiger Struktur, das aus dem Tiefseeschwamm Leiodermatium sp. isoliert wurde, zeigt proliferationshemmende Aktivität gegen mehrere Krebszelllinien sowie drastische Effekte auf die Spindelbildung in mitotischen Zellen. Das ungewöhnliche Polyketidgerüst und stereochemische Konfiguration des Moleküls wurden durch eine Kombination experimentellen computergestützten NMR-Methoden ermittelt.
It is well established that females mount stronger immune responses than males, but only very little understood about the underlying mechanisms. We have analyzed local cytokine differences among intact females, those had been ovariectomized (OVX), receiving estrogen replacement after OVX, and both before production of delayed-type hypersensitivity (DTH) responses. report confirmation a much larger DTH response in versus males. However, OVX resulted an even response, while smaller when...
Pancreatic cancer presents one of the most negative prognosis all cancers as it has usually metastasized by time a patient is diagnosed. The American Cancer Society estimates that 93% patients will die within 5 years diagnosis, highlighting need for new drugs to treat this disease. Interleukin 8 (IL-8) mediates angiogenesis tumors arising from Ras mutations, which are present in about 90% pancreatic adenocarcinomas. Overexpression IL-8 believed promote tumor and activate survival signaling...
Cryptosporidium sp. are apicomplexan parasites that cause significant morbidity and possible mortality in humans valuable livestock. There no drugs on the market effective population most severely affected by this parasite. This study is first high-throughput screen for potent anti-Cryptosporidium natural products sourced from a unique marine compound library. The Harbor Branch Oceanographic Institute at Florida Atlantic University has collection of diverse organisms some which have been...