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Nowadays, deaths from neoplasms are at the top of the World Health Organization list. The interest of scientists is focused on the search for natural substrates perspective for the targeted anticancer chemotherapy. Antarctic yeasts represent an unexplored object regarding their antineoplastic potential. The studies in the present work demonstrated the capacity of Sporobolomyces salmonicolor AL36 for cell growth in different cultivation processes. During the transfer of small-scale flasks cultivation to the bioreactor system, optimal biomass quantities of approximately 6.0 g/L were recorded. A comparative examination of the metabolic profiles of the two extracts tested reveals differences in the synthesized molecules corresponding to different cytotoxicity (antineoplastic activity) in vitro on malignant cell lines. The median inhibitory concentration (IC50) of each extract determined by the MTT test was used as a parameter for evaluating the antiproliferative effects. Most sensitive to the in vitro effect of the extract of Sp. salmonicolor AL36 cultivated in flasks was the cell line SKW-3 (T cell leukemia, derivative of KE-37) - IC50 = 35.3 µg/ml, while the bioreactor biomass extract was most cytotoxic for RPMI-8226 (multiple myeloma) cells - IC50 = 28.27µg/ml. The proteome analysis of treated and untreated malignant cells showed that both yeast extracts have a strong potential to inhibit anti-apoptotic proteins which reveals a mode of action related to induction of apoptosis and proliferation inhibition.

Antarctic is among the most scarcely investigated extreme niches in relation to microorganisms living there and synthesis of unusual molecules for adaptation to extremely low temperatures, lack of water availability and precipitation, numerous freeze–thaw cycles, strong wind levels and high sublimation, evaporation and ultraviolet radiation. Several yeast genera such as Cryptococcus, Mrakia, Candida, Rhodotorula, Leucosporidium, Debaryomyces have been described as part of the biodiversity of the continent. The aim of the present research was to studying yeast variety in the Livingston Island, Antarctica, and yeast potential to synthesize extracellular polysaccharides. Thanks to the cooperation of the Bulgarian Antarctic Expedition, three different strains were isolated and identified. Based on a genetic analysis of ITS1-5.8S-ITS4 regions of rRNA they were related to two genera – Cystobasidium and Vishniacozima. One of the strains belonged to the species Cystobasidium ongulense and two to Vishniacozima victoriae. The morphological differences of the two species included the color of the colonies - red and cream, respectively, while both species were glossy and with a smooth edge. Cystobasidium ongulense cells were larger and elongated. The differences between the species also included the different number of assimilated carbon sources. The ITS domains of the rRNA gene were amplified using the universal primers ITS1 and ITS4. The process of extracellular polymer biosynthesis was performed at a cultivation temperature of 21°C±1°C. The cell growth over 5.5gL-1 and exopolysaccharide production from 1.6 to 3.6gL-1 were registered at 120th h of the fermentation process. Based on sampling of soil, moss or penguin feathers in Bulgarian base, the Livingston Island, new results for yeast diversity were accumulated and they can contribute to the fundamental worldwide knowledge on the biodiversity of the Antarctic continent. Unusual origin of exopolysaccharides synthesized by the isolates and their valuable preliminary characterized properties suggest a possibility for their biotechnological exploration. Nowadays, deaths from neoplasms are at the top of the World Health Organization list. The interest of scientists is focused on the search for natural substrates perspective for the targeted anticancer chemotherapy. Antarctic yeasts represent an unexplored object regarding their antineoplastic potential. The studies in the present work demonstrated the capacity of Sporobolomyces salmonicolor AL36 for cell growth in different cultivation processes. During the transfer of small-scale flasks cultivation to the bioreactor system, optimal biomass quantities of approximately 6.0 g/L were recorded. A comparative examination of the metabolic profiles of the two extracts tested reveals differences in the synthesized molecules corresponding to different cytotoxicity (antineoplastic activity) in vitro on malignant cell lines. The median inhibitory concentration (IC50) of each extract determined by the MTT test was used as a parameter for evaluating the antiproliferative effects. Most sensitive to the in vitro effect of the extract of Sp. salmonicolor AL36 cultivated in flasks was the cell line SKW-3 (T cell leukemia, derivative of KE-37) - IC50 = 35.3 µg/ml, while the bioreactor biomass extract was most cytotoxic for RPMI-8226 (multiple myeloma) cells - IC50 = 28.27µg/ml. The proteome analysis of treated and untreated malignant cells showed that both yeast extracts have a strong potential to inhibit anti-apoptotic proteins which reveals a mode of action related to induction of apoptosis and proliferation inhibition.

Experimental evaluation of the antineoplastic activity and mode of action of alkylphosphocholines with special emphasize on the intravenous injectable erufosine was made on malignant cells of hematological origin, as well as from breast cancer and urinary bladder cancer. The synthetic alkylating antimetabolite bendamustine was found to be a selective inducer of apoptosis in lymphoid malignant cells with unexpectedly low clastogenic activity. The biotechnologically obtained lignan justicidin B possesses pronounced antitumor effects in vitro at concentrations that can be reached in vivo without any signs of toxicity. It overcomes multidrug resistance associated with the expression of MRP1. There are data obtained about the antineoplastic activity of a glycopeptide of ramnolipid kind and a biosurfactant from Pseudomonas aeruginosa and Nocardia farcinica, respectively. Two mesoporous drug delivery systems were studied when loaded with budesonide, silver and curcumin. Modulation of the damage caused by differentiated eosinophil cells and enhancement of the antitumor activity were recorded. Curcumin included in electrospun polymeric mats was found to keep its pharmacological activity. An in vitro model of multiple myeloma bone damage was established and characterized immunohistochemically. An animal model of diabetes in hypertensive rats after streptozotocin destruction of the pancreatic beta-cells was established and validated. Neuro- and hepatotoxicity were estimated for several, Извършена е експериментална оценка на антинеопластичната активност и механизма на действие на алкилфосфохолини с акцент върху венозно приложимия Erufosine при малигнени клетки с хематологичен произход, както и от рак на млечната жлеза и на пикочния мехур. Синтетичният алкилиращ антиметаболит Bendamustine е селективен индуктор на апоптоза при лимфоидни малигнени клетки с необичайно ниска кластогенна активност. Биотехнологично полученият лигнан юстицидин Б притежава изразени противотуморни ефекти in vitro при достижими без прояви на токсичност концентрации in vivo. Преодолява резистентността обусловена от експресията на MRP1. Получени са данни за антинеопластична активност на един гликопептид от рамнолипиден тип и на един биосърфактант от Pseudomonas aeruginosa и Nocardia farcinica. Изследвани са две мезопорести лекраство-доставящи системи, натоварени с Budesonide, сребро и куркумин като е установено повлияване на увреждането от диференцирани еозинофилни клетки и усилване на противотуморната активност. Включен в електроовлакнени полимерни матове куркумин запазва фармакологичната си активност. Създаден и имунохистохимично охарактеризиран е in vitro модел на костната лезия при мултиплен миелом. Създаден и валидиран е животински модел на захарен диабет при хипертензивни плъхове след стрепотозотоцинова деструкция на бета-клетките в панкреаса. Оценена е невротоксичността и хепатотоксичността на няколко серии съединения с антихолинестеразна и противотуберкулозна активност.