Synthesis, characterization, in vitro cytotoxic activity and molecular docking of dinuclear gold(I) complexes with terephthalaldehyde bis(thiosemicarbazones)

Four new bis(thiosemicarbazones) were synthesized and, by reaction with AuI, four dinuclear gold(I) complexes were obtained. Cytotoxic activity of both the ligands and the complexes against NCI-H460 (lung), A2780 and A2780cisR (ovarian) cancer cell lines and normal renal LLC-PK1 cells has been evaluated. The results indicate that the ligands do not show antiproliferative activity in the cell lines evaluated and the NCI-H460 line is only sensitive to the complex bearing cyclohexyl substituents. On the other hand, the four complexes display high cytotoxic activity towards A2780 and A2780 cisR and the complex with thiosemicarbazide could circumvent resistance to cisplatin. By contrast, none of the complexes show significant inhibition against the normal renal cell line LLC-PK1. Docking studies with carboxamide ribonucleotide formyltransferase (AICARFT) and cyclin-dependent kinases (CDK2) for lung and ovarian cancer, respectively, show that the best binding affinity corresponds to complex 4, which is in agreement with the in vitro cytotoxicityThe authors thank MICINN, Instituto de Salud Carlos III, for funding (Project PS09/00963) and Red de Excelencia MetalBio (CTQ2017-90802-REDT

Synthesis, antimicrobial activity and molecular docking of di‐ and triorganotin (IV) complexes with thiosemicarbazide derivatives

"This is the peer reviewed version of the following article: Applied Organometallic Chemistry 33.2 (2019): e4700, which has been published in final form at https://doi.org/10.1002/aoc.4700. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions"Six organotin (IV) complexes with two ligands derived from 2,3‐butanedione and thiosemicarbazide have been synthesized and fully characterized by several spectroscopic techniques, including 119Sn NMR and single crystal X‐ray diffraction. Reactions of the ligand diacetyl‐2‐(thiosemicarbazone)‐3‐(3‐ hydroxy‐2‐naphthohydrazone), L1 H2, with SnR2Cl2 (R = Me, Bu, Ph) lead to the obtaining of complexes 1–3 with general formula [SnR2L1 ] (R = Me 1, R = Bu 2, R = Ph 3), in which the ligand is doubly deprotonated and behaves as a N2SO donor, whereas from the reactions of diacetyl‐2‐thiosemicarbazone, HATs, with the same organotin precursors any complex could be isolated. By contrast, reaction of HATs with SnR3Cl induces the ligand cyclization to form a 1,2,4‐triazine‐3‐thione that binds to the metal as a monoanionic donor in a mono or bidentate manner to form compounds 4–6 with formula [SnR3L2 ] (R = Me 4, R = Bu 5, R = Ph 6). The antimicrobial activity of the ligands and the six complexes was tested towards bacteria and fungi, including clinical isolated strains. The results show that the ligands are devoid of activity, except HATs that displays activity against Bacillus subtilis. Conversely, the complexes exhibit good antimicrobial properties against Gram positive and negative bacteria, yeasts and moulds. The best results are obtained for complexes [SnBu3L2 ] 5 and [SnPh3L2 ] 6, indicating that their more lipophilic nature could play an important role in the ease of microbial cell penetration. In some cases, these complexes display similar or higher activity than that of ampicillin and miconazole, used as antibacterial and antifungal positive controls, respectively. Docking study with DHPS protein (S. aureus) has shown that out of six drugs, the compound 6 has the best binding affinity (−8.5 Kcal/mol)Secretaría de Estado de Investigación, Desarrollo e Innovación, Grant/Award Number: CTQ2017‐90802‐RED

Differential White Blood Cell Count and Type 2 Diabetes: Systematic Review and Meta-Analysis of Cross-Sectional and Prospective Studies

Objective: Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated.Research Design and Methods: Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored.Results: The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10(-18)). Substantial heterogeneity was present (I-2 = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10(-4)), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10(-13)), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10(-5)). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference.Conclusions: A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate

Chaotic Variations of AES Algorithm

ABSTRACT Advanced Encryption Standard (AES) algorithm is considered a