Marine Antitumor Peptide Dolastatin 10: Biological Activity, Structural Modification and Synthetic Chemistry

Dolastatin 10 (Dol-10), a leading marine pentapeptide isolated from the Indian Ocean mollusk Dolabella auricularia, contains three unique amino acid residues. Dol-10 can effectively induce apoptosis of lung cancer cells and other tumor cells at nanomolar concentration, and it has been developed into commercial drugs for treating some specific lymphomas, so it has received wide attention in recent years. In vitro experiments showed that Dol-10 and its derivatives were highly lethal to common tumor cells, such as L1210 leukemia cells (IC50 = 0.03 nM), small cell lung cancer NCI-H69 cells (IC50 = 0.059 nM), and human prostate cancer DU-145 cells (IC50 = 0.5 nM), etc. With the rise of antibody-drug conjugates (ADCs), milestone progress was made in clinical research based on Dol-10. A variety of ADCs constructed by combining MMAE or MMAF (Dol-10 derivatives) with a specific antibody not only ensured the antitumor activity of the drugs themself but also improved their tumor targeting and reduced the systemic toxicity. They are currently undergoing clinical trials or have been approved for marketing, such as Adcetris®, which had been approved for the treatment of anaplastic large T-cell systemic malignant lymphoma and Hodgkin lymphoma. Dol-10, as one of the most medically valuable natural compounds discovered up to now, has brought unprecedented hope for tumor treatment. It is particularly noteworthy that, by modifying the chemical structure of Dol-10 and combining with the application of ADCs technology, Dol-10 as a new drug candidate still has great potential for development. In this review, the biological activity and chemical work of Dol-10 in the advance of antitumor drugs in the last 35 years will be summarized, which will provide the support for pharmaceutical researchers interested in leading exploration of antitumor marine peptides.

Short communication: Environment and morphometric of sea hare Dolabella auricularia from shrimp pond, Sorong, West Papua, Indonesia

Sofian A, Suhermanto A, Saidin, Sayuti M, Novianto D, Widyasari F. 2021. Short communication: Environment and morphometric of sea hare Dolabella auricularia from shrimp pond, Sorong West Papua, Indonesia. Biodiversitas 22: xxxx. Dolabella auricularia is a herbivorous marine biota living on the shallow seabed, which is found mostly in Indo-Pacific waters. The purpose of this study was to analyze the environmental and morphometric characteristics of Dolabella auricularia which live in vaname shrimp pond, Sorong, West Papua, Indonesia. Samples were collected from April to June 2020. From the measurement of pond waters environmental conditions, the following data were obtained: temperatures ranging from 31.47 ± 1.08oC, salinity ranging from 31.91 ± 2.29 ppt, pH ranging from 8.02 ± 0.20, brightness 108.00 ± 45.63 cm, and Dissolved Oxygen (DO) ranging from 4.10 ± 0.22 mg/L. The morphometrics of D. auricularia consisted of R-Anterior resp distances with sizes ranging from 38.9 ± 17 mm, wet weight ranging from 170 ± 34 g total lengths ranging from 112 ± 57.83 mm, posterior diameters ranging from 71 ± 41 mm. D. auricularia was found in pond waters as a pest for shrimp culture. However, D. auricularia also has biomedical and economic potentials as raw materials for the pharmaceutical industry. So, further studies are needed for their development.

Investigation of Chemical Composition and Antibacterial Activity of Ink from Sea Hare Dolabella auricularia

This study was conducted to determine the chemical composition of ink from sea hare (Dolabella auricularia) of Pujada Bay, City of Mati, Davao Oriental. The proximate and mineral composition were determined by using the standard official methods of the Association of Official Analytical Chemists (AOAC). The presence of secondary metabolites was investigated by using different qualitative tests, namely Froth test (saponins), Libermann-Buchard (sterols), Bate-Smith and Metacalf (flavonoids), Dragendorff and Maeyer (alkaloids), Keller-kiliani (glycoside), ferric chloride (tannins) and Bortnträger (anthraquinones). Its antibacterial activity against Escherichia coli and Staphylococcus aureus was determined by using agar well diffusion method. The results for proximate analyses showed that ink contained 90.4 % moisture, 2.044 % ash, 5.324 % crude fat and 0.75 % protein. The mineral analyses were 0.25 % phosphorous, 578 µg/g potassium, 0.662 % sodium, 310.8 µg/g calcium, 664 µg/g magnesium, 2.146 µg/g iron and 1.898 µg/g zinc. Secondary metabolites screening revealed that ink contained saponins, steroids and flavonoids. Further, the ink extract showed weak antibacterial factor. This is the first study conducted on the ink of sea hare in Davao region and its preliminary results showed that it is a good source of primary and secondary metabolites. These findings can be added to the potential medicinal value of sea hare and a basis for further chemical studies that will hopefully lead to the discovery of compounds with pharmacological importance.

AN ETHNOGRAPHY ON THE WEDGE SEA HARE IN MACTAN ISLAND, THE PHILIPPINES (ETNOGRAFI TENTANG KELINCI LAUT DI PULAU MACTAN, FILIPINA)

The wedge sea hare (Dolabella auricularia) is a mollusk species found in tidal flats and is consumed as food around the Philippines. The practice of consuming its internal organs is probably found only on the Mactan Island. The Problem of this study is to clarify why people collect the internal organs of wedge sea hare. The objective is a gleaner who have special skills to identify the sea hare burrows. Participatory observation and measurement method were employed for this research. As a result, it found that the gleaners precisely identify occupied sea hare burrows using unique skills, and to remove the edible internal organs from the disposable body. Local people regard the internal organs as a nutrition. As a conclusion, this practice must be an adaptation to an environment where vegetable protein is scarce due to a limestone-based soil unsuitable for agriculture. Thus, the role of the wedge sea hare in a unique culture was also developed.Kelinci laut (Dolabella auricularia) adalah spesies moluska yang ditemukan di dataran pasang surut dan dikonsumsi sebagai makanan di sekitar Filipina. Praktik mengkonsumsi organ internalnya mungkin hanya ditemukan di Pulau Mactan. Masalah penelitian ini adalah untuk menjelaskan mengapa orang mengumpulkan organ internal kelinci laut. Tujuannya adalah seorang pengumpul yang memiliki keterampilan khusus untuk mengidentifikasi lubang kelinci laut. Metode pengamatan dan pengukuran partisipatif digunakan untuk penelitian ini. Sebagai hasilnya, ditemukan bahwa para pengumpul secara tepat mengidentifikasi lubang yang didiami kelinci laut dengan menggunakan keterampilan unik, dan mengeluarkan organ internal yang dapat dimakan dari tubuh yang bisa dibuang. Masyarakat lokal menganggap organ dalam sebagai nutrisi. Sebagai kesimpulan, praktik ini harus merupakan adaptasi terhadap lingkungan di mana protein nabati langka karena tanah berbahan dasar batugamping yang tidak cocok untuk pertanian. Dengan demikian, peran kelinci laut dalam budaya unik juga dikembangkan.

An account of the occurrence of Wedge Sea Hare Dolabella auricularia (Lightfoot, 1786) (Gastropoda: Aplysiidae) from Andaman Islands, India

In the present article we provide a detailed account on the occurrence of Wedge Sea Hare Dolabella auricularia, from two different locations (Hut Bay and Burmanallah) of Andaman Islands. This species has been reported by Rao (2003) from Andamans but there is no specific location mentioned. First occurrence of this species was observed in Hut Bay coast of Little Andaman and after a three month interval a group of Wedge Sea Hares were again spotted from Burmanallah, South Andaman. In the present article we have given a detailed account on the occurrence and morphological features with field and laboratory pictures of D. auricularia and its biomedical importance based on literature.