Discovery of cytotoxic natural products from Red Sea sponges: Structure and synthesis

Khan, Safia; Al-Fadhli, Ammar A.; Tilvi, Supriya

doi:10.1016/j.ejmech.2021.113491

Cited by 11 publications

(4 citation statements)

References 97 publications

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“…[ 15 ] To determine the role of the cytoskeleton in the regulation of the Hippo pathway by chiral hydrogels, we first used Lat B to disrupt the cytoskeleton, an inhibitor of the F‐actin. [ 16 ] The cells were cultured on different chiral hydrogels for 48 h and then treated with 2.5 u m latrunculin B (Lat B) for 1 h. By measuring the stiffness of the cells by AFM, we confirmed that Lat B can significantly reduce the Young's modulus of the cells (Figure S6, Supporting Information). Phalloidin staining showed that cytoskeletal structure resulted in a punctate distribution following treatment with Lat B, which is in agreement with the depolymerization of F‐actin (Figure 5e; Figure S7, Supporting Information).…”

Section: Resultsmentioning

confidence: 83%

Chiral Hydrogel Accelerates Re‐Epithelization in Chronic Wounds via Mechanoregulation

Zhu

Xing

Dou

et al. 2022

Adv Healthcare Materials

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Chronic wounds, such as diabetic foot ulcers (DFU), are a serious clinical problem. It is a challenge for the conventional wound dressings to achieve the desirable therapeutic efficacy due to the lack of biomimetic structural environment for rapid re-epithelization. Inspired by the naturally existing chiral structures in skin, a novel amino acid-based chiral hydrogel dressing is developed, consisting of left-handed or right-handed helical fibers self-assembled by l/d-phenylalanine derivatives. Compared to the levorotatory chiral hydrogel (LH), the dextral chiral hydrogel (DH) shows the ability to enhance cell adhesion, proliferation, and migration, and strongly promotes diabetic wound healing and re-epithelialization with a drug-free mode. Interestingly, the dextral chiral hydrogel is able to actively increase adsorption of type I collagen and promote proliferation and migration of keratinocyte in an integrin and YAP-mediated manner. This study not only provides a novel strategy for treatment of chronic wounds by utilizing dextral chiral hydrogel dressings, but also unveils the molecular mechanism for effect of dextral chiral structures on the promoted proliferation of keratinocyte.

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Section: Resultsmentioning

confidence: 83%

Chiral Hydrogel Accelerates Re‐Epithelization in Chronic Wounds via Mechanoregulation

Zhu

Xing

Dou

et al. 2022

Adv Healthcare Materials

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“…Cancer is the second deadliest illness and has obtained enormous attention from researchers, who are trying to understand mechanisms of this disease and to find new drugs for therapy [40]. Marine sponges and their sponge-associated organisms represent precious sources of natural products with cytotoxic activity [41][42][43]. Two indole alkaloids, topsentin (see Figure 1) and bromotopsentin, were isolated from different species of sponges belonging to the genus Spongosorites (Spongosorites sp.…”

Section: Biotechnological Activities Of Compounds Isolated From Demos...mentioning

confidence: 99%

Marine Demospongiae: A Challenging Treasure of Bioactive Compounds

et al. 2022

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In the last decades, it has been demonstrated that marine organisms are a substantial source of bioactive compounds with possible biotechnological applications. Marine sponges, in particular those belonging to the class of Demospongiae, have been considered among the most interesting invertebrates for their biotechnological potential. In this review, particular attention is devoted to natural compounds/extracts isolated from Demospongiae and their associated microorganisms with important biological activities for pharmacological applications such as antiviral, anticancer, antifouling, antimicrobial, antiplasmodial, antifungal and antioxidant. The data here presented show that this class of sponges is an exciting source of compounds, which are worth developing into new drugs, such as avarol, a hydroquinone isolated from the marine sponge Disidea avara, which is used as an antitumor, antimicrobial and antiviral drug.

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“…Marine natural products (MNPs) are regarded as important sources for the discovery of lead compounds for anti-cancer drugs, due to their unique chemical structures and diverse biological activities [23]. Simplifying complex structures of natural products, while retaining the desired biological activity, is a valid and meaningful strategy in the drug development process [24,25]. This strategy has been successfully used in the lead optimization of MNPs and yielded a number of marketed drugs and drug candidates [26,27].…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel Inhibitor of TfR1 from Designed and Synthesized Muriceidine A Derivatives

Mai

et al. 2022

Antioxidants

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The transferrin receptor 1 (TfR1) plays a key role in cellular iron uptake through its interaction with iron-bound Tf. TfR1 is often reported to be overexpressed in malignant cells, and this increase may be associated with poor prognosis in different types of cancer, which makes it an attractive target for antitumor therapy. The marine natural product Muriceidine A is a potent anticancer agent reported in our previous work. In this study, we designed and synthesized a series of Muriceidine A derivatives and described the systematic investigation into their cytotoxic activities against four tumor cells. Most of the derivatives showed stronger antitumor activity and we found that the introduction of electron-donating groups at position C-2 of unsaturated piperidine was beneficial to anticancer activity and unsaturated piperidine was responsible for the antiproliferative activity. Among these compounds, 12b (methyl at position C-2 of unsaturated piperidine) exhibited the strongest cytotoxicity against MDA-MB-231 cells. Further pharmacological research showed that 12b bound to Transferrin receptor 1 (TfR1) directly caused iron deprivation and ROS imbalance along with the degradations of several oncoproteins, especially FGFR1, through the proteasome pathway; thus, inducing cell cycle arrest and apoptosis in MDA-MB-231 breast cancer cells. Our findings indicate that 12b is a promising lead compound targeting TfR1 for triple negative breast cancer.

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Discovery of cytotoxic natural products from Red Sea sponges: Structure and synthesis

Cited by 11 publications

References 97 publications

Chiral Hydrogel Accelerates Re‐Epithelization in Chronic Wounds via Mechanoregulation

Chiral Hydrogel Accelerates Re‐Epithelization in Chronic Wounds via Mechanoregulation

Marine Demospongiae: A Challenging Treasure of Bioactive Compounds

Identification of a Novel Inhibitor of TfR1 from Designed and Synthesized Muriceidine A Derivatives

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