Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties.

A series of 1″-(alkylsulfonyl)-dispiro[indoline-3,2'-pyrrolidine-3',3″-piperidine]-2,4″-diones 6a‒o has been synthesized through regioselective multi-component azomethine dipolar cycloaddition reaction of 1-(alkylsulfonyl)-3,5-bis(ylidene)-piperidin-4-ones 3a‒h. X-ray diffraction studies (6b‒d,h) confirmed the structures. The majority of the synthesized analogs reveal promising antiproliferation properties against a variety of human cancer cell lines (MCF7, HCT116, A431 and PaCa2) with good selectivity index towards normal cell (RPE1). Some of the synthesized agents exhibit potent inhibitory properties against the tested cell lines with higher efficacies than the standard references (sunitinib and 5-fluorouracil). Compound 6m is the most potent. Multi-targeted inhibitory properties against EGFR and VEGFR-2 have been observed for the synthesized agents. Flow cytometry supports the antiproliferation properties and shows the tested agents as apoptosis and necrosis forming. Vero cell viral infection model demonstrates the anti-SARS-CoV-2 properties of the synthesized agents. Compound 6f is the most promising (about 3.3 and 4.8 times the potency of the standard references, chloroquine and hydroxychloroquine). QSAR models explain and support the observed biological properties.

Development of Isatin-Based Schiff Bases Targeting VEGFR-2 Inhibition: Synthesis, Characterization, Antiproliferative Properties, and QSAR Studies.

Three sets of isatin-based Schiff bases were synthesized utilizing the molecular hybridization approach. Some of the synthesized Schiff bases show significant to moderate antiproliferative properties against MCF7 (breast), HCT116 (colon), and PaCa2 (pancreatic) cancer cell lines with potency compared to reference drugs 5-fluorouracil (5-FU) and Sunitinib. Among all, compound 17 f (3-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino)-1-((1-(2-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methylindolin-2-one) exhibits promising antiproliferative properties against the MCF7 cancer cell line with 2.1-fold more potency than Sunitinib. However, among all the synthesized compounds, three (5-methylisatin derivatives) were the most effective against HCT116 in comparison to 5-FU. Compound 17 f exhibited the highest anti-angiogenic effect on the vasculature as it significantly reduced BV from 43 mm to 2 mm in comparison to 5.7 mm for Sunitinib and flow cytometry supports the arrest of the cell cycle at G1/S phases. In addition, compound 17 f also showed high VEGFR-2 inhibition properties against breast cancer cell lines. Robust 2D-QSAR studies supported the biological data.

"TPGS surface modified bilosomes as boosting cytotoxic oral delivery systems of curcumin against doxorubicin resistant MCF-7 breast cancer cells".

The goal of this work was to design nude bilosomes (Bil) and D-alpha-tocopheryl polyethylene glycol succinate (TPGS) surface coated bilosomes as an oral delivery platform for improving the antitumor activity and poor oral permeability of Curcumin (CUR). Twelve different formulae were acquired from 31.22 factorial analysis considering different independent variables: bile salt type; Sodium taurocholate (STC) or Sodium cholate (SC) and weight percent; 1% or 5 % W/W, both at 2 levels respectively, while Span 60:Cholesterol ratio at 3 levels (1:1, 5:1, 9:1). Following optimization, the selected optimum formula was picked up based on the favorable minimum particle size (187.2 ± 2.2 nm), maximum zeta potential value (-41.3 ± 2.2 mV) and maximum entrapment efficiency (93.4 ± 5.1%) which was further coated with TPGS. The mean fluorescence intensity (MFI) of CUR permeated from the optimum TPGS-F7 and CUR-Bil (F7) formulae exhibited 6.6 and 3.4 folds increase respectively adopting ex-vivo duodenal permeation assay relative to that of CUR suspension. Moreover, the cellular uptake efficiency via the established Caco-2 cells revealed that the uptake of CUR was 61.9 ± 5.3% and 34.76 ± 0.61% from TPGS-F7 and CUR-Bil (F7) relative to the uptake efficiency of CUR suspension (7.4 ± 2.12%). Coherently, TPGS-CUR-Bil showed excellent response expressed in dominant reduction in IC50 value (2.8 ± 0.07 µg/ml) against multidrug resistant (MDR) tumors following 48 h incubation of Doxorubicin Resistant Breast Cancer (MCF-7/ADR) cell lines.

Synthesis of aspirin-curcumin mimic conjugates of potential antitumor and anti-SARS-CoV-2 properties.

Series of piperidone-salicylate conjugates were synthesized through the reaction of 3E,5E-bis(arylidene)-4-piperidones with the appropriate acid chloride of acetylsalicylate in the presence of triethylamine. All the synthesized conjugates reveal antiproliferative properties against A431 (squamous skin) cancer cell line with potency higher than that of 5-fluorouracil. Many of the synthesized agents also exhibit promising antiproliferative properties against HCT116 (colon) cancer cell line, of which 5o and 5c are the most effective with 12.9, 9.8 folds potency compared with Sunitinib. Promising activity is also shown against MCF7 (breast) cancer cell line with 1.19, 1.12 folds relative to 5-fluorouracil. PI-flow cytometry of compound 5c supports the arrest of cell cycle at G1-phase. However, compound 5o and Sunitinib arrest the cell cycle at S-phase. The synthesized conjugates can be considered as multi-targeted tyrosine kinase inhibitors due to the promising properties against VEGFR-2 and EGFR in MCF7 and HCT116. CDOCKER studies support the EGFR inhibitory properties. Compounds 5p and 5i possessing thienylidene heterocycle are anti-SARS-CoV-2 with high therapeutic indices. Many of the synthesized agents show enhanced COX-1/2 properties than aspirin with better selectivity index towards COX-2 relative to COX-1. The possible applicability of the potent candidates discovered as antitumor and anti-SARS-CoV-2 is supported by the safe profile against normal (non-cancer, RPE1 and VERO-E6) cells.

3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2.

Sets of 3-alkenyl-2-oxindoles (6,10,13) were synthesized in a facile synthetic pathway through acid dehydration (EtOH/HCl) of the corresponding 3-hydroxy-2-oxoindolines (5,9,12). Single crystal (10a,c) and powder (12a,26f) X-ray studies supported the structures. Compounds 6c and 10b are the most effective agents synthesized (about 3.4, 3.3 folds, respectively) against PaCa2 (pancreatic) cancer cell line relative to the standard reference used (Sunitinib). Additionally, compound 10b reveals antiproliferative properties against MCF7 (breast) cancer cell with IC50 close to that of Sunitinib. CAM testing reveals that compounds 6 and 10 demonstrated qualitative and quantitative decreases in blood vessel count and diameter with efficacy comparable to that of Sunitinib, supporting their anti-angiogenic properties. Kinase inhibitory properties support their multi-targeted inhibitory activities against VEGFR-2 and c-kit in similar behavior to that of Sunitinib. Cell cycle analysis studies utilizing MCF7 exhibit that compound 6b arrests the cell cycle at G1/S phase while, 10b reveals accumulation of the tested cell at S phase. Compounds 6a and 10b reveal potent antiviral properties against SARS-CoV-2 with high selectivity index relative to the standards (hydroxychloroquine, chloroquine). Safe profile of the potent synthesized agents, against normal cells (VERO-E6, RPE1), support the possible development of better hits based on the attained observations.

Biphenylurea/thiourea derivatives tagged with heteroarylsulfonamide motifs as novel VEGFR2 inhibitors; Design, synthesis and anti-angiogenic activity.

Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has emerged as a vital tool for cancer treatment. In this study, a new series of biphenylurea/thiourea derivatives tagged with heteroarylsulfonamide motifs (3a-l) was designed and synthesized as novel VEGFR2 inhibitors. The biochemical profiles of the target compounds were investigated using viability of human umbilical vascular endothelial cells (HUVECs), migration assay and Western blot using sorafenib as reference antiangiogenic drug. Most of the tested compounds exhibited significant antiproliferative activity against HUVECs, where compounds 3a, 3e, 3g, 3h and 3l exhibited better antiproliferative activity than sorafenib. All compounds significantly inhibited VEGF stimulated migration of HUVECs at 10 µM dose with (3a, 3e, 3g, 3h and 3l) showing better or comparable inhibitory activities to that of sorafenib. Moreover, Western blotting analysis confirmed antiangiogenic effect of those compounds with significant reduction in the level of VEGFR-2 compared to sorafenib. Finally, cytotoxicity screening of these derivatives against four cancer cells and RPE1 as normal cell line was performed. The mechanistic effectiveness in cell cycle progression and apoptotic induction were evaluated for the promising compound 3e due to its remarkable cytotoxic activity against tested cancer cell lines and significant VEGFR-2 inhibition. Flow cytometric analysis showed that compound 3e induced cell growth arrest at G2/M phase and stimulated the apoptotic death of HepG2 cells.

Fluoroquinolone-3-carboxamide Amino Acid Conjugates: Synthesis, Antibacterial Properties And Molecular Modeling Studies.

BACKGROUND: Bacterial infections are considered as one of the major global health threats, so it is very essential to design and develop new antibacterial agents to overcome the drawbacks of existing antibacterial agents. METHODS: The aim of this work is to synthesize a series of new fluoroquinolone-3-carboxamide amino acid conjugates by molecular hybridization. We utilized benzotriazole chemistry to synthesize the desired hybrid conjugates. RESULTS: All the conjugates were synthesized in good yields, characterized, evaluated for their antibacterial activity. The compounds were screened for their antibacterial activity using methods adapted from the Clinical and Laboratory Standards Institute. Synthesized conjugates were tested for activity against medically relevant pathogens; Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27856) Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis (ATCC 19433). CONCLUSION: The observed antibacterial experimental data indicates the selectivity of our synthesized conjugates against E.Coli. The protecting group on amino acids decreases the antibacterial activity. The synthesized conjugates are non-toxic to the normal cell lines. The experimental data were supported by computational studies.

A Naturally Derived Carrier for Photodynamic Treatment of Squamous Cell Carcinoma: In Vitro and In Vivo Models.

Photodynamic therapy (PDT) is a non-invasive treatment strategy that includes the combination of three components-a photosensitizer, a light source, and tissue oxygen. PDT can be used for the treatment of skin diseases such as squamous cell carcinoma. The photosensitizer used in this study is the naturally derived chlorophyll derivative chlorin e6 (Ce6), which was encapsulated in ultradeformable ethosomes. Singlet oxygen production by Ce6 upon laser light irradiation was not significantly affected by encapsulation into ethosomes. PDT of squamous cell carcinoma cells treated with Ce6 ethosomes triggered increased mitochondrial superoxide levels and increased caspase 3/7 activity, resulting in concentration- and light-dose-dependent cytotoxicity. Ce6 ethosomes showed good penetration into 3D squamous cell carcinoma spheroids, which upon laser light irradiation exhibited reduced size, proliferation, and viability. The PDT effect of Ce6 ethosomes was specific and showed higher cytotoxicity against squamous cell carcinoma spheroids compared to normal skin fibroblast spheroids. In addition, PDT treatment of squamous cell carcinoma xenografts grown on chorioallantoic membranes of chick eggs (CAM) exhibited reduced expression of Ki-67 proliferation marker and increased terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining, indicating reduced proliferation and activation of apoptosis, respectively. The results demonstrate that Ce6-loaded ethosomes represent a convenient formulation for photodynamic treatment of squamous cell carcinoma.

New acrylamide-sulfisoxazole conjugates as dihydropteroate synthase inhibitors.

New functionalized acrylamide derivatives bearing sulfisoxazole moiety were designed to target bacterial dihydropteroate synthase (DHPS). The in vitro antimicrobial activities of these compounds were assessed. The E-configuration of compound 5b was proved by single crystal X-ray analysis. Compounds 5g and 5h displayed double the activity of ampicillin against B. subtilis. Also, 5h was two times more active than gentamycin against E. coli. Interestingly, compounds 5f-g, 7c, 8a, 8c exhibited two folds the potency of amphotericin B against S. racemosum while 5h displayed three folds the activity of amphotericin B against S. racemosum. Most of the synthesized compounds showed superior activities to the parent sulfisoxazole and were non-toxic to normal cells. DHPS is confirmed to be a putative target for our compounds via antagonizing their antibacterial activity by the folate precursor (p-aminobenzoic acid) and product (methionine) on E. coli ATCC 25922. Docking experiments against DHPS rationalized the observed antibacterial activity. Additionally, compound 5g was evaluated as a selective targeting vector for 99mTc that showed a remarkable uptake and targeting ability towards the infection site that was induced in mice.

Synthesis and molecular modeling studies of cholinesterase inhibitor dispiro[indoline-3,2'-pyrrolidine-3',3''-pyrrolidines].

A set of dispiro[indoline-3,2'-pyrrolidine-3',3''-pyrrolidines] 8a-l was regioselectively synthesized utilizing multi-component azomethine cycloaddition reaction of 3-(arylmethylidene)pyrrolidine-2,5-diones 5a-e, isatins 6a-c and sarcosine 7. Single crystal X-ray studies of 8c add conclusive support for the structure. Compounds 8e and 8g reveal cholinesterase inhibitory properties with promising efficacy against both AChE and BChE and were found to be more selective towards AChE than BChE as indicted by the selectivity index like Donepezil (a clinically used cholinesterase inhibitory drug). Molecular modeling studies assist in understanding the bio-observations and identifying the responsible parameters behind biological properties.

Design, synthesis, antimicrobial, and DNA gyrase inhibitory properties of fluoroquinolone-dichloroacetic acid hybrids.

A series of new fluoroquinolone conjugates 8a-g and 9a-f were synthesized via benzotriazole-mediated synthetic approach with good yield and purity. Some of the synthesized analogs exhibited significant antibacterial properties against Escherichia coli and Staphylococcus aureus with potency higher than that of the parent drugs through in vitro standard bioassay procedure (conjugates 8c and 8d reveal antimicrobial properties with potency 1.9, 61.9, 20.7 and 2.4, 37.1, 8.3 folds relative to the parent antibiotic 6 against E. coli, S. aureus, and Enterococcus faecalis, respectively). The observed experimental data were supported by enzymatic DNA gyrase inhibitory property. Developed BMLR-QSAR model validates the observed experimental data and recognizes the parameters responsible for the enhanced antibacterial properties.

Novel thiazolidines: Synthesis, antiproliferative properties and 2D-QSAR studies.

A series of N-substituted (Z)-2-imino-(5Z)-ylidene thiazolidines/thiazolidin-4-ones were synthesized and their antiproliferative activities against colon (HCT-116) and breast (MCF7) cancer cell lines were evaluated utilizing an MTT growth assay. A 2D-QSAR investigation was conducted to probe and validate the obtained antiproliferative properties for the thiazolidine derivatives. The majority of the thiazolidines exhibit higher potency against a colon cancer cell line relative to the standard reference. The p-halophenylimino p-anisylidene derivatives exhibited the highest anti-proliferative activity against HCT116 relative to control (IC50 = 8.9-10.0 µM compared to 20.4 µM observed for 5-fluorouracil as positive control). An X-ray study confirmed the Z, Z'-configurations for two examples of the synthesized compounds.

Ethosomes and lipid-coated chitosan nanocarriers for skin delivery of a chlorophyll derivative: A potential treatment of squamous cell carcinoma by photodynamic therapy.

Photodynamic therapy (PDT) is a localized treatment strategy used for skin cancers such as squamous cell carcinoma (SCC), the second most common form of skin cancer. PDT combines a photosensitizer, laser source and tissue oxygen. In this study, the selected photosensitizer, ferrous chlorophyllin (Fe-CHL) was loaded in ethosomes and lipid coated chitosan (PC/CHI) nanocarriers to enhance skin delivery of Fe-CHL for potential PDT of squamous carcinoma. The nanocarrier formulations were characterized and studied for their skin retention and penetration depth of Fe-CHL across mouse skin ex vivo using high performance liquid chromatography and confocal microscopy. Confocal microscope images of mouse skin showed deeper penetration of ethosomes down to the dermis when compared to PC/CHI that was confined to the epidermis, although they showed no significant difference in skin retention. Immunohistochemistry (IHC) staining with ki67 and TUNEL show maintained skin structure and no cytotoxic effects of the nanocarrier gel formulations before laser exposure to mouse skin. The nanocarriers were also studied for their PDT effect against human SCC monolayer and three-dimensional (3-D) spheroids. When compared to ethosomes, PC/CHI showed higher cytotoxicity in MTT assay and live confocal microscopy showed cell disintegration after laser exposure. For 3-D spheroids, PC/CHI also showed higher cytotoxicity using acid phosphatase assay and a decrease in spheroid size was observed using light microscopy. In conclusion, both types of nanocarriers can be used for their potential treatment of SCC using PDT depending on the tumour localization in the skin.

Novel Curcumin Inspired Antineoplastic 1-Sulfonyl-4-Piperidones: Design, Synthesis and Molecular Modeling Studies.

BACKGROUND: Curcumin is a well-known example of plant origin exhibiting promising diverse biological properties such as, anti-inflammatory and antitumor as well as poor pharmacokinetic/pharmacodynamic properties. This is why effective agents based on its chemical scaffold were explored. METHODS: A set of 3,5-bis(ylidene)-1-(alkylsulfonyl)piperidin-4-ones were synthesized in excellent yield (80- 96%) through dehydrohalogenation reaction of 3,5-bis(ylidene)-4-piperidinones with the corresponding alkane sulfonyl chloride in the presence of triethylamine. Antiproliferative properties of the synthesized compounds (dienone/curcumin inspired analogues) were studied by the standard MTT technique. RESULTS: Most of the synthesized compounds revealed antiproliferative properties against HCT116 (colon) and A431 (skin/squamous) cancer cell lines with IC50 values at sub-micromolar level. Compound 36 also exhibited potency against MCF7 (breast) and A549 (lung) cancer cell lines (IC50 = 2.23, 4.27µM, respectively) higher than that of the reference standards (IC50 = 3.15, 5.93µM for 5-fluorouracil and doxorubicin against MCF7 and A549 cell lines, respectively). Cytotoxic properties of the synthesized compounds against non-cancer RPE1 cell line supported the safety profile of the effective agents against normal cells. Molecular modeling (3Dpharmacophore and 2D-QSAR) studies validated the observed bio-properties and explained the parameters governing activity. Inhibitory properties of compounds 27 and 29 (representative examples of the promising antiproliferative agents synthesized) supported their mode of action against topoisomerase IIα. CONCLUSION: The synthesized scaffold is a promising antitumor agent (with special selectivity against colon and skin/squamous cancer cell lines) so, it can be considered for further investigation and development of highly effective hits/leads based on the computational models obtained.

Synthesis, computational studies, antimycobacterial and antibacterial properties of pyrazinoic acid-isoniazid hybrid conjugates.

Benzotriazole and microwave mediated syntheses led to a new set of hybrid conjugates of pyrazinoic acid with isoniazid via amino acid linkers in excellent yields with retention of chirality. Microbiological screening of the synthesized conjugates revealed an exceptionally high activity against some of the pathogenic bacterial strains at low concentrations. Promising antimycobacterial properties were observed against tuberculous and non-tuberculous mycobacteria. Robust molecular models (2D-QSAR and 3D-pharmacophore) support the observed biological properties. Safety profile of the synthesized conjugates against human normal cell (RPE1) was evaluated by MTT technique.

Synthesis, human topoisomerase IIα inhibitory properties and molecular modeling studies of anti-proliferative curcumin mimics.

3,5-Bis(arylidene)-N-substituted-4-oxo-piperidine-1-carboxamides 24-51 were synthesized as curcumin mimics in a facile pathway through reaction of 3,5-bis(arylidene)-4-piperidones with the appropriate isocyanate in the presence of triethylamine. The 3E,5E'-stereochemical configuration was conclusively supported by single crystal X-ray studies of compounds 25 and 34. Most of the synthesized piperidinecarboxamides showed high anti-proliferative properties with potency higher than that of 5-fluorouracil (clinically approved drug against colon, breast and skin cancers) through in vitro MTT bio-assay. Some of them revealed anti-proliferative properties at sub-micromolar values (IC50 = 0.56-0.70 µM for compounds 29, 30 and 34-38 against HCT116; and IC50 = 0.64 µM for compound 30 against A431 cell lines) with promising inhibitory properties against human DNA topoisomerase IIα. The safe profile of the anti-proliferative active agents against the RPE1 normal cell line may prove their selectivity towards carcinoma cells. Robust molecular models (2D-QSAR, 3D-pharmacophore) supported the SAR and validated the observed bio-properties.

Novel hydrazide-hydrazone and amide substituted coumarin derivatives: Synthesis, cytotoxicity screening, microarray, radiolabeling and in vivo pharmacokinetic studies.

The current work presents the synthesis and biological evaluation of new series of coumarin hydrazide-hydrazone derivatives that showed in vitro broad spectrum antitumor activities against resistant pancreatic carcinoma (Panc-1), hepatocellular carcinoma (HepG2) and leukemia (CCRF) cell lines using doxorubicin as reference standard. Bromocoumarin hydrazide-hydrazone derivative (BCHHD) 11b showed excellent anticancer activity against all tested cancer cell lines. Enzyme assays showed that BCHHD 11b induced apoptosis due to activation of caspases 3/7. Moreover, 11b inhibited GST and CYP3A4 in a dose dependent manner and the induced cell death could be attributed to metabolic inhibition. Moreover, 11b microarray analysis showed significant up- and down-regulation of many genes in the treated cells related to apoptosis, cell cycle, tumor growth and suppressor genes. All of the above presents BCHHD 11b as a potent anticancer agent able to overcome drug resistance. In addition, compound 11b was able to serve as a chemical carrier for 99mTc and the in vivo biodistribution study of 99mTc-11b complex revealed a remarkable targeting ability of 99mTc into solid tumor showing that 99mTc-11b might be used as a promising radiopharmaceutical imaging agent for cancer.

Synthesis, antitumor evaluation and microarray study of some new pyrazolo[3,4-d][1,2,3]triazine derivatives.

Design and synthesis of new anticancer scaffolds; pyrazolo[3,4-d][1,2,3]triazine derivatives, is a promising solution to overcome drug resistance problem. A series of (E)-2-cyano-N-(aryl)-3-methylthio-3-(substituted-amino)acrylamides 3a-e was synthesized and transformed to the 3-aminopyrazole derivatives 4a-e which were then transformed to the target pyrazolotriazinones 6a-e. All compounds were evaluated for their anticancer activity against three different cancer cell lines namely Huh-7, Panc-1 and CCRF. Compounds 3a, 3c, 6a and 6c showed excellent anticancer activity against Huh-7 cell line (IC50: 4.93-8.84 µM vs doxorubicin 5.43 µM). Similarly, compounds 6a and 6d showed excellent activities against Panc-1 cells (IC50: 9.91 µM and 4.93 µM vs doxorubicin 6.90 µM). Caspase-Glo 3/7 assay was done and the results revealed that the pro-apoptotic activity of the target compounds could be due to the stimulation of caspases 3/7. Microarray experiment for Huh-7 cells treated with 6c was performed to search for other molecular changes. SLC26A3, UGT1A1, UGT2B15, UGT2B7, DNASE1, MUCDH1 and UGT2B17 were among the up-regulated genes, while, GIP3, TAGL, THBS1, IFI27, FSCN1 and SOCS2 were among the most extensively down-regulated genes. These genes belong to apoptosis, metabolism, cell cycle, tumor growth and suppressor genes. Finally, pyrazolo[3,4-d][1,2,3]triazine derivatives could be potent anticancer drugs in the future.

Comparative Correlation Between Chemical Composition and Cytotoxic Potential of the Coral-Associated Fungus Aspergillus sp. 2C1-EGY Against Human Colon Cancer Cells.

Cancer is a leading cause of death in several countries. In the search for new anticancer drugs, marine organisms have played an important role in the discovery of lead compounds and the development of new pharmaceuticals for their wide diversity of chemical structures and biological activities. In the present study, the cytotoxicity on colorectal cancer cells HCT116 exerted by marine fungus Aspergillus sp. 2C1-EGY extracts associated with the soft coral Sinularia sp. was investigated; the sub-fractions Fr 2c and Fr 2d had significantly high cytotoxic activity (88 and 85%, respectively). Moreover, the major hexadecanoic, octadecanoic, and octadecenoic acids as well as their methyl esters were isolated. GC/MS analysis revealed the identification of 46 major and minor compounds, from which 19 saturated and unsaturated fatty acids and eight fatty acid esters were identified.

Investigating on the Correlation Between Some Biological Activities of Marine Sponge-Associated Bacteria Extracts and Isolated Diketopiperazines.

Marine organisms have been considered as the richest sources of novel bioactive metabolites, which can be used for pharmaceutical purposes. In the last years, the interest for marine microorganisms has grown for their enormous biodiversity and for the evidence that many novel compounds isolated from marine invertebrates are really synthesized by their associated bacteria. Nevertheless, the discovery of a chemical communication Quorum sensing (QS) between bacterial cells and between bacteria and host has gained the researchers to expand the aim of their study toward the role of bacteria associated with marine invertebrates, such as marine sponge. In the present paper, we report the evaluation of biological activities of different extracts of bacteria Vibrio sp. and Bacillus sp. associated with marine sponges Dysidea avara and Ircinia variabilis, respectively. Moreover, we evaluated the biological activities of some diketopiperazines (DKPs), previously isolated, and able to activate QS mechanism. The results showed that all extracts, fractions, and DKPs showed low scavenging activity against DPPH and superoxide anion, low cytotoxic and anti-tyrosinase activities, but no antimicrobial and acetylcholinesterase inhibitory activities. One DKP [cyclo-(trans-4-hydroxy-L-prolyl-L-leucine)] has the highest α-glucosidase inhibitory activity even than the standard acarbose.