Synthesis and evaluation of novel 2,4-disubstituted arylthiazoles against T. brucei.

The design, synthesis and pharmacological evaluation of the 4-substituted-2-[3-(adamant-1-yl)-4-fluorophenyl]thiazoles 1a-j, the 4-substituted-2-[4-(adamant-1-yl)phenyl]thiazoles 2a-h, the 2-substituted-4-[4-(adamant-1-yl)phenyl]thiazoles 3a-e, the N-substituted 2-phenylthiazol-4-ethylamides 4a, b and the N-substituted 4-phenylthiazol-2-ethylamides 4c, d is described. Compounds 1a and 2a exhibit trypanocidal activity in the range of IC50 = 0.42 μM and IC50 = 0.80 μM, respectively. Both of these derivatives bear a lipophilic end, which consists of a 4-(1-adamantyl) phenyl or a 3-(1-adamantyl)phenyl moiety, a 1,3-thiazole ring and a functional end, which comprises of an alkylamine and can be considered as promising candidates for the treatment of Trypanosoma brucei infections

Synthesis of diphenoxyadamantane alkylamines with pharmacological interest.

In this work, the synthesis and the pharmacological evaluation of diphenoxyadamantane alkylamines Ia-f and IIa-f is described. The new diphenoxy-substituted adamantanes share structural features present in trypanocidal and antitubercular agents. 1-Methylpiperazine derivative Ia is the most potent against T. brucei compound, whilst its hexylamine congener IIf exhibits a significant antimycobacterial activity

Unpublished Mediterranean and Black Sea records of marine alien, cryptogenic, and neonative species

To enrich spatio-temporal information on the distribution of alien, cryptogenic, and neonative species in the Mediterranean and the Black Sea, a collective effort by 173 marine scientists was made to provide unpublished records and make them open access to the scientific community. Through this effort, we collected and harmonized a dataset of 12,649 records. It includes 247 taxa, of which 217 are Animalia, 25 Plantae and 5 Chromista, from 23 countries surrounding the Mediterranean and the Black Sea. Chordata was the most abundant taxonomic group, followed by Arthropoda, Mollusca, and Annelida. In terms of species records, Siganus luridus, Siganus rivulatus, Saurida lessepsianus, Pterois miles, Upeneus moluccensis, Charybdis (Archias) longicollis, and Caulerpa cylindracea were the most numerous. The temporal distribution of the records ranges from 1973 to 2022, with 44% of the records in 2020–2021. Lethrinus borbonicus is reported for the first time in the Mediterranean Sea, while Pomatoschistus quagga, Caulerpa cylindracea, Grateloupia turuturu, and Misophria pallida are first records for the Black Sea; Kapraunia schneideri is recorded for the second time in the Mediterranean and for the first time in Israel; Prionospio depauperata and Pseudonereis anomala are reported for the first time from the Sea of Marmara. Many first country records are also included, namely: Amathia verticillata (Montenegro), Ampithoe valida (Italy), Antithamnion amphigeneum (Greece), Clavelina oblonga (Tunisia and Slovenia), Dendostrea cf. folium (Syria), Epinephelus fasciatus (Tunisia), Ganonema farinosum (Montenegro), Macrorhynchia philippina (Tunisia), Marenzelleria neglecta (Romania), Paratapes textilis (Tunisia), and Botrylloides diegensis (Tunisia).peer-reviewe

ΣΧΕΔΙΑΣΜΟΣ, ΣΥΝΘΕΣΗ ΚΑΙ ΑΠΟΤΙΜΙΣΗ ΤΗΣ ΑΝΤΙΤΡΥΠΑΝΟΣΩΜΙΑΚΗΣ ΔΡΑΣΗΣ ΝΕΩΝ ΑΔΑΜΑΝΤΑΝΙΚΩΝ ΘΕΙΑΖΟΛΙΩΝ

Στην παρούσα εργασία περιγράφεται ο σχεδιασμός, η σύνθεση και η φαρμακολογική αξιολόγηση της δράσης κατά του T. brucei, νέων αδαμαντανικών θειαζολίων. Συγκεκριμένα, σχεδιάστηκαν και συντέθηκαν τα 4-υποκατεστημένα-2-[3-(αδαμαντ-1-υλο)-4-φθοροφαινυλο]θειαζόλια 12 και 13a-i. Για την επίδραση της υποκατάστασης του αδαμαντανίου στον αρωματικό δακτύλιο των προηγούμενων ενώσεων και τη διευθέτηση της 4-υποκατεστημένης θειαζολικής πλάγιας αλυσίδας στο χώρο, σε σχέση με την αντιτρυπανοσωμιακή δράση, συντέθηκαν τα ομόλογα 4-υποκατεστημένα-2-[4-(αδαμαντ-1-υλο-φαινυλο]θειαζόλια 18 και 19a-c. Επιπλέον, μελετήθηκε η επίδραση στη δραστικότητα της μεταβολής της σχετικής θέσης των υποκαταστατών του θειαζολικού πυρήνα, μέσω των ανολόγων 2-αιθυλενο-4-[4-(αδαμαντ-1-υλο)φαινυλο]θειαζόλια 31c,d. Επίσης, εξετάστηκε η σχέση της απόστασης του τελικού κατιονικού κέντρου από το θειαζόλιο, με τη δραστικότητα, μέσω του αμινοθειαζολίου 31a και του αμινομεθυλενοθειαζολίου 31b. Ο προκαταρκτικός φαρμακολογικός έλεγχος ανέδειξε σημαντική αντιτρυπανοσωμιακή δράση της αμίνης 12 (IC50 420nM)In the context of the present MSc dissertation, the design, synthesis and pharmacological evaluation, against T. brucei, of a series of novel adamantane thiazoles is described. Specifically, the 4-substituted-2-[3-(adamant-1-yl)-4-flurophenyl]thiazoles 12 and 13a-i were designed and synthesized. In order to test the effect of the adamantane substitution of the aromatic ring, as well as the spatial arrangement of the side thiazole chain on to the antitrypanosomial activity, the homologues 4-substituted-2-[4-(adamant-1-yl-phenyl]thiazoles 18, και 19a-c were synthesized. Additionally, the 2-ethylene-4-[4-(adamant-1-yl)phenyl]thiazoles 31c,d were designed and synthesized in an attempt to probe how the antirypanosomial activity is affected when the substituents of the thiazole moiety interchanged positions. Moreover, the effect of the distance between the polar cationic head and the thiazole moiety, on the antiparasitic activity, was tested via the aminothiazole 31a and the aminomethylethiazole 31b. The preliminary pharmacological evaluation revealed the potency of the amine 12 (IC50 420 nM)

Sigma Receptor (σR) Ligands with Antiproliferative and Anticancer Activity

Sigma receptor (σR) ligands have proven to be useful as cancer diagnostics and anticancer therapeutics and their ligands have been developed as molecular probes in oncology. Moreover, various σR ligands generate cancer cell death in vitro and in vivo. These σR ligands have exhibited promising results against numerous human and rodent cancers and are investigated under preclinical and clinical study trials, indicating a new category of drugs in cancer therapy

Design, Synthesis and in vitro Controlled Release of New Adamantanodiarylketone Antimycobacterials

In the present investigation, the synthesis, the biology and the development of matrix tablet formulations for the in vitro controlled release of new adamantane diarylketone antimycobacterial derivatives, is presented. In the skeleton of the new compounds, a diarylketone, functionalized by a 2-hydroxypropylenoxy-3-butylamine, a 2-hydroxypropylenoxy-3-hexylamine and a 1-(2-hydroxyoctyl)piperidin-4-yl moiety, is incorporated at the C-1 adamantane position. The new derivatives were tested against the H37Rv Mycobacterium tuberculosis strain and exhibited satisfactory activity. In view of their lipophilic character, it was intriguing to examine their in vitro dissolution profile in buffer solutions simulating the gastric and intestinal environments. To this end, matrix tablets of the most active compound, {4-[(adamantan-1-yl)phenyl-4-(3-(butylamino)-2-hydroxypropoxy)]phenyl}methanone (A), incorporating the appropriate excipients, were prepared using the direct compression method. The preliminary test results show that its dissolution profile is in alignment with the desired pattern for the per os administration of tuberculocidal agents

Unpublished Mediterranean and Black Sea records of marine alien, cryptogenic, and neonative species

To enrich spatio-temporal information on the distribution of alien, cryptogenic, and neonative species in the Mediterranean and the Black Sea, a collective effort by 173 marine scientists was made to provide unpublished records and make them open access to the scientific community. Through this effort, we collected and harmonized a dataset of 12,649 records. It includes 247 taxa, of which 217 are Animalia, 25 Plantae and 5 Chromista, from 23 countries surrounding the Mediterranean and the Black Sea. Chordata was the most abundant taxonomic group, followed by Arthropoda, Mollusca, and Annelida. In terms of species records, Siganus luridus, Siganus rivulatus, Saurida lessepsianus, Pterois miles, Upeneus moluccensis, Charybdis (Archias) longicollis, and Caulerpa cylindracea were the most numerous. The temporal distribution of the records ranges from 1973 to 2022, with 44% of the records in 2020–2021. Lethrinus borbonicus is reported for the first time in the Mediterranean Sea, while Pomatoschistus quagga, Caulerpa cylindracea, Grateloupia turuturu, and Misophria pallida are first records for the Black Sea; Kapraunia schneideri is recorded for the second time in the Mediterranean and for the first time in Israel; Prionospio depauperata and Pseudonereis anomala are reported for the first time from the Sea of Marmara. Many first country records are also included, namely: Amathia verticillata (Montenegro), Ampithoe valida (Italy), Antithamnion amphigeneum (Greece), Clavelina oblonga (Tunisia and Slovenia), Dendostrea cf. folium (Syria), Epinephelus fasciatus (Tunisia), Ganonema farinosum (Montenegro), Macrorhynchia philippina (Tunisia), Marenzelleria neglecta (Romania), Paratapes textilis (Tunisia), and Botrylloides diegensis (Tunisia)