Synthesis and biological evaluation of platinum complexes of highly functionalized aroylaminocarbo-N-thioyl prolinate containing tetrahydropyrrolo[3,4-c]pyrrole-1,3(2H,3aH)-dione moieties

Platinum complexes, derived from two families of bidentate funcionalized aroylaminocarbo-N-thyoyl prolinates, are prepared using mild conditions from prolinates, which are available via 1,3-dipolar cycloadditions. The resulting four coordinated neutral square-planar platinum(II) complexes are very stable and are fully characterized. Their structures are determined by spectroscopic and analytical methods and one of them by single crystal X-ray diffraction analysis. In this pattern, the platinum exhibits distorted square planar geometry, with cis-bond angles ranging from 89.42(2) and 94.37(6)° and trans-bond angles of 176.19(6) and 177.08(6)°, respectively. Anti(myco)bacterial and antifungal studies of all these new compounds are carried out under standardized protocols.This work is a part of Samet Belveren's ongoing PhD thesis granted by Mersin University (Project no. BAP-SBE TEB(SB) 2017-2-TP3-2564). We gratefully acknowledge financial support from Mersin University and the Spanish Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC), the Spanish Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, EU) (projects CTQ2016-76782-P and CTQ2016-81797-REDC), the Generalitat Valenciana (PROMETEOII/2014/017), University of Alicante and Mersin University (Project. MEU-2017-COL-01007-M150D)

Synthesis of highly functionalized 2-(pyrrolidin-1-yl)thiazole frameworks with interesting antibacterial and antimycobacterial activity

A versatile, facile and concise approach to access to highly substituted functionalized 2-(pyrrolidin-1-yl)thiazole ring system is accomplished. The efficient protocol proceeds by the reaction of corresponding racemic or enantiomerically enriched pyrrolidines and readily available benzoylisothiocyanate in acetonitrile followed by sequential reaction of readily available alpha-bromo ketones in acetone. The selectivity and good yield in the desired product is another important advantage of this reaction protocol. In a few cases, the resulting N-benzoylthiourea intermediate cyclizes spontaneously before reacting with the benzophenone component. Finally, a wide study of the biological scope of this new bisheterocyclic molecules is reported.This work is a part of Samet Belveren's ongoing PhD thesis granted by Mersin University (Project no. BAP-SBE TEB(SB) 2017-2-TP3-2564). The authors thank Mersin University (Turkey) and the University of Alicante for support. We also thank the Scientific and Technological Research Council of Turkey (TÜBİTAK), the Spanish Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC), the Spanish Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, EU) (projects CTQ2016-76782-P, and CTQ2016-81797-REDC), the Generalitat Valenciana (PROMETEOII/2014/017), (Consolider Ingenio 2010, CSD2007-00006) for research financing

From Bioactive Pyrrolidino[3,4-c]pyrrolidines to more Bioactive Pyrrolidino[3,4-b]pyrrolidines via Ring-Opening/Ring-Closing Promoted by Sodium Methoxide

The process involving a rearrangement of pyrrolidino[3,4-c]pyrrolidine to another pyrrolidino[3,4-b]pyrrolidine using sodium methoxide as base is fully studied. The effects of the substituents are analyzed during the ring-opening/ring-closing sequence. Computational studies are also performed to explain the importance of susbstituents and quaternary carbons, especially when the (3-indolyl)methyl is present in the starting material. Finally, all the samples are evaluated as potential candidates for antibacterial and antimycobacterial activities.We are grateful for support from Mersin University [Project no: MEU-2017-COL-01007-M150D and BAP-SBE AKB (SB) 2012-8 YL and BAP 2015- AP2-1342]. We gratefully acknowledge financial support from the Spanish Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC), the Spanish Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, EU) (projects CTQ2016-76782-P and CTQ2016-81797-REDC), the Generalitat Valenciana (PROMETEOII/2014/017), the Gobierno Vasco/Eusko Jaurlaritza (GV/EJ, grant IT673-13), and the University of Alicante. O.L. gratefully acknowledges UPV/EHU for her postdoctoral grant. O.L. and A.d.C. gratefully thank SGI/IZO-SGIker and DIPC for generous allocation of computational resources

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

A series of novel palladium(II) and nickel(II) complexes of multifunctionalized aroylaminocarbo-N-thioylpyrrolinates were synthesized and characterized by analytical and spectroscopic techniques. The biological properties of the freshly prepared compounds were screened against S. aureus, B. subtilis, A. hydrophila, E. coli, and A. baumannii bacteria and antituberculosis activity against M. tuberculosis H37Rv strains. Also, the antifungal activity was studied against C. albicans, C. tropicalis, and C. glabrata standard strains. A deep conformational survey was monitored using DFT calculations with the aim to explain the importance of the final conformation in the biological experimental results.This work is a part of Samet POYRAZ's ongoing Ph.D. thesis granted by Mersin University (Project no. 2019-1-TP3-3463). We gratefully acknowledge financial support from Çukurova University and Mersin University (Project no. 2020-1-AP4-3982). We gratefully acknowledge financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (projects CTQ2016-81893REDT, and RED2018-102387-T) the Spanish Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, EU) (projects CTQ2016-76782-P, CTQ2016-80375-P, CTQ2017-82935-P and PID2019-107268GB-I00), the Generalitat Valenciana (IDIFEDER/2021/013, CIDEGENT/2020/058)

Synthesis, structure and bioactivity of a mononuclear octahedral [Prolinate2-Na(MeOH)4]−H+ complex

The synthesis of a mononuclear octahedral [Prolinate2-Na(MeOH)4]−H+ complex is achieved from a [3 + 2] cycloadduct with excess of NaOMe in methanol. The slow crystallization provides the hexacoordinated complex stabilized by four molecules of solvent. The antibacterial, antifungal and anti-tuberculosis activity of this compound is also evaluated.This work is a part of Samet Belveren's ongoing PhD thesis granted by Mersin University (Project no. BAP-SBE TEB(SB) 2017-2-TP3-2564). We gratefully acknowledge financial support from Mersin University and the Spanish Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC), the Spanish Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, EU) (projects CTQ2016-76782-P and CTQ2016-81797-REDC), the Generalitat Valenciana (PROMETEOII/2014/017), University of Alicante and Mersin University (Project. MEU-2017-COL-01007-M150D)

Phytochemical analysis and biological activities of Salvia candidissima subsp. candidissima mericarps

The sterol, amino acid, mineral, total phenolic, and total flavonoid contents, and the antioxidant, antimicrobial, and antibiofilm activities of Salvia candidissima subsp. candidissima mericarps were investigated. The mericarps were collected in the province of Bayburt, Turkey. Gas chromatography was used for sterol analysis, Prominence ultra-fast liquid chromatography for amino acid analysis, and ICPMS for mineral analysis. Folin-Ciocalteu, Al(NO3 )3 , and DPPH radical scavenging activity assays were performed on ethanol extracts of the mericarps to evaluate the total phenolic and flavonoid contents, and antioxidant potential, respectively. The ethanol and hexane extracts of the mericarps were tested for their antimicrobial activity against seven bacterial and three fungal strains using the microdilution method and for antibiofilm activity against Pseudomonas aeruginosa biofilm using the crystal violet staining method. The sterol, amino acid, and mineral contents and antibiofilm activity of the mericarps were studied for the first time. The most abundant components of the mericarps are determined as β-sitosterol (69.8%), glutamic acid (4895 mg/100 g), and potassium (11474 µg/g). The results of total phenolic and flavonoid contents and DPPH free radical scavenging activity were 3.47 µg GAE/mg extract, 0.35 µg QE/mg extract, and 79.79%, respectively. Both of the tested extracts exhibited antimicrobial activity against all the tested microorganisms, however, the efficiency of the extracts was not as strong as the reference drugs ampicillin and fluconazole. While both extracts were effective in preventing biofilm formation, the ethanol extract was found to be more effective than the hexane extract in preformed biofilm inhibition. In conclusion, S. candidissima subsp. candidissima mericarps have good nutritional potential with high amounts of amino acids, sterols (especially β-sitosterol), minerals, and phenolics and flavonoids. Additionally, our findings provide important preliminary data for the literature in terms of the antibiofilm activity of Salvia candidissima subsp. candidissima mericarps

Determination of Acid Dissociation Constants ( p

The acid dissociation constants of potential bioactive fused ring thiohydantoin-pyrrolidine compounds were determined by potentiometric titration in 20% (v/v) ethanol-water mixed at 25±0.1°C, at an ionic background of 0.1 mol/L of NaCl using the HYPERQUAD computer program. Proton affinities of potential donor atoms of the ligands were calculated by AM1 and PM3 semiempiric methods. We found, potentiometrically, three different acid dissociation constants for 1a–f. We suggest that these acid dissociation constants are related to the carboxyl, enol, and amino groups

N-Benzoylthiourea-pyrrolidine carboxylic acid derivatives bearing an imidazole moiety: Synthesis, characterization, crystal structure, in vitro ChEs inhibition, and antituberculosis, antibacterial, antifungal studies

A series of novel N-benzoylthiourea-pyrrolidine carboxylic acid derivatives bearing an imidazole moiety has been prepared and their various biological activities are evaluated. The ability of forming intermolecular hydrogen-bonds of these molecules was pursued in the search of the best antimicrobial activity. The synthesized compounds were tested to search whether they had an enzyme inhibitory potency against AChE and BChE, which are the main targets for Alzheimer's disease. The prepared compounds were also screened for antituberculosis activity against M. tuberculosis H37Rv strain and the antibacterial activity against E. coli, A. baumannii, S. aureus, B. subtilis, A. hydrophila, bacteria. In addition, their antifungal activities are also evaluated against C. tropicalis, C. albicans, C. glabrata strains.This work is a part of Samet POYRAZ's Ph.D. thesis granted by Mersin University (Project no: 2019-1-TP3-3463) and (Project no: 2020-1 AP4-3982). We also gratefully acknowledge support from Çukurova University (Project no: TSA-2021-13814), Alicante University and Mersin University

Study of the anti(myco)bacterial and antitumor activities of prolinate and N-amidocarbothiolprolinate derivatives based on fused tetrahydropyrrolo[3,4-c]pyrrole-1,3(2H,3aH)-dione, bearing an indole ring

WOS: 000449934300013A series of prolinate and N-amidocarbothiolprolinate derivatives based on a fused pyrrole-3,4-dione core, bearing indole ring systems, are prepared from the corresponding amino acid and an aldehyde via thermal 1,3-dipolar cycloaddition of azomethine ylides and condensation with benzoylisothiocyanate. Products are fully characterized by NMR, FT-IR, MS, and an X-ray crystal structure. The prepared compounds are screened for their antibacterial activity against a range of Gram-positive and Gram-negative bacteria and their antimycobacterial activity against M. tuberculosis H37Rv strain. In addition, two selected target compounds are evaluated for cytotoxicity, apoptosis, and anti-inflammatory effects on MCF-7 (breast carcinoma) cell lines. The incorporation of indole ring and -C(O)NHC(S)- moiety resulted to be beneficial since the biological point of view. [GRAPHICS]Mersin University, Research Foundation [BAP 2015-AP2-1342]We would like to thank Mersin University, Research Foundation (Project No: BAP 2015-AP2-1342) for financial support