الفهرس 
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Abstract
In this study, six different types of sponge samples were collected from marine environment, Red Sea and Mediterranean Sea, which taxonomically identified as Amphimedon ochracea, Hyrtios erecta, undescribed species of Amphimedon, Ircinia echinata, Ircinia muscarum and Ircinia fasciculate. A total of 17 symbiotic bacterial isolates were isolated and purified from these samples. The selected phenotypically different bacterial isolates representing the community structure in different types of sponges were examined to determine their ability to produce active antimicrobials against tested pathogenic bacteria (Gram-positive and Gram-negative bacteria) and fungi. Their activities were tested using the well-cut diffusion technique to test the ability of the bacterial isolates to inhibit the growth of tested pathogenic bacteria. After incubation period 24 hr, the diameter of inhibition zone around each well was determined. Five isolates from 17 symbiotic bacterial isolates revealed the maximum antimicrobial activity against tested pathogenic bacteria and fungi. Two of these most promising bacterial isolates (R4 and R14) were isolated from Hyrtios erecta and Amphimedon ochracea, respectively, showed the highest activities and selected to complete the next experiments as potent organisms, since they showed the highest diameter of inhibition zone (antimicrobial agent production) on both tested pathogenic bacteria and fungi. On the other hand, the crude extracts of the tested five bacterial extracts showed growth inhibition effects against the tested 3 cell lines, Hepatocellular carcinoma (HepG2), Breast cancer (MCF-7) and Colon cancer (HCT-116). The extract of bacterial isolate (R4) showed the most promising cytotoxic activity against (MCF-7, IC50 16.5 µg/ml) and (HCT-116, IC50 20.3 µg/ml), while (R14) showed the highest activity against (HepG2, IC50 19.6 µg/ml). The bacterial isolates were identified based on the phylogenetic analysis of the nucleotide sequences of their 16S rRNA genes. The most potent bacterial isolate (R4, R14) were deposited in the National Center for Biotechnology Information (NCBI) database and identified to Bacillus gottheilii MSB1 and Bacillus gottheilii MSB2, under certain accession numbers [KU199821] and [KU199822], respectively. According to antimicrobial and cytotoxicity screening, the most potent bacterial isolate Bacillus gottheilii MSB1 (BGMSB1) that showed strong antimicrobial and anticancer activity was chosen for further studies, including the characterization of its bioactive secondary metabolites, thus this strain was cultivated in liquid ISP2 medium under optimized conditions, the supernatant was used for successive extraction with different solvents of different polarities, n-Hexane (H), Dichloromethane (DCM), Ethyl acetate (E) and n-Butanol (B), yielded four fractions from BGMSB1 supernatant, all the tested extracts showed growth inhibition effects against the different 3 cell lines used in the study, the bacterial extract DCM showed the most promising strong cytotoxic activity against (HepG2, IC50 30.8 µg/ml); (MCF-7, IC50 59.7 µg/ml) and (HCT-116, IC50 43.2 µg/ml), but extract B showed a weak cytotoxic activity against (HepG2, IC50 186 µg/ml); (MCF-7, IC50 231 µg/ml) and (HCT-116, IC50 233 µg/ml), while the Doxorubicin Reference Standard was found to be as follows: (HepG2, 0.47 0.04 µg/ml); (MCF-7, 0.44 0.03 µg/ml); (HCT-116, 0.469 0.07 µg/ml). The natural product most potent extract was dichloromethane Bacillus gottheilii MSB1 extract (DCMBGMSB1-extract), due to the presence of high content of promising classes of phenolic compounds, unsaturated fatty acid and esters, pyrrolopyrazine alkaloids, N-sulfonyl azetidine derivatives, 4H-pyran derivatives, 2,4,6-Trioxohexahydropyrimidine derivatives (barbituric acid derivatives).