Túlio Ricardo Couto de Lima Souza

Indole-thiosemicarbazones have different biological activities. The present study evaluated the preliminary interaction of these compounds with biomolecules, specifically human serum albumin (HSA) and DNA, using fluorescence techniques. The suppression results (K_sv) for HSA ranged from 3.5 x 10⁴ to 4.6 x 10⁵ L/mol, while for DNA, they ranged from 1.4 x 10⁴ to 5.9 x 10⁴ L/mol. The suppression was classified as weak to strong for HSA and moderate for DNA. The bimolecular suppression constant (K_q) showed values between 6.0 x 10¹² and 8.2 x 10¹³ L/mol/s for HSA and from 1.4 x 10¹² to 5.9 x 10¹² L/mol/s for DNA, suggesting a static suppression mechanism. Compound PR09 stood out, presenting a binding constant (K_a) greater than 10⁵ L/mol for HSA, indicating a strong interaction. Additionally, PR05, PR06, PR07, and PR09 demonstrated strong interactions with DNA. The values of the number of binding sites (n) indicated that PR01, PR02, and PR09 bind to multiple sites on HSA, while PR04, PR05, PR06, and PR09 interact with more than one site on DNA. All interactions were spontaneous, with ∆G negative. The distance between the compounds and tryptophan on HSA was less than 8 nm, suggesting high energy transfer efficiency. In molecular docking studies, PR05 showed the highest affinity for DNA (-11.15 kcal/mol), while PR09 had the highest affinity for HSA (-10.00 kcal/mol). PR07 exhibited the lowest binding energies for DNA (-8.21 kcal/mol) and for HSA (-7.38 kcal/mol). This study demonstrates that the evaluated compounds have potential as new drug candidates.

Cancer is a complex and multifactorial disease characterized by uncontrolled cell growth and is one of the main causes of death in the world. This work aimed to evaluate a small series of 10 different indole-thiosemicarbazone compounds as potential antitumor agents. This is a pioneering study. For this, the antioxidant and cytotoxic capacity against normal and tumor cells was evaluated. The results showed that the compounds were able to promote moderate to low antioxidant activity for the ABTS radical scavenging assay. ADMET in silico assays showed that the compounds exhibited good oral bioavailability. As for toxicity, they were able to promote low cytotoxicity against normal cells, in addition to not being hemolytic. The compounds showed promising in vitro antitumor activity against the T47D, MCF-7, Jurkat and DU-145 strains, not being able to inhibit the growth of the Hepg2 strain. Through this in vitro study, it can be concluded that the compounds are potential candidates for antitumor agents.

Objective The present study assesses the implementation and the impact after 2 years of a school-based human papillomavirus (HPV) vaccination program in a Brazilian city. Methods A prospective study assessing the implementation of the program, offering quadrivalent HPV vaccine in two annual doses to girls and boys aged from 9 to 10 years old. The program was started in the city of Indaiatuba, state of São Paulo, Brazil, in 2018, and had authorization from the National Immunization Program. The number of HPV vaccine first doses applied and the coverage in 2018 was calculated and compared to the year 2017. There were described events that have influenced the results. Results The program invited 4,878 children through schools (87.1% of the target population), and 7.5% refused vaccination. Several concurrent events required or competed for health professionals of the vaccination teams. The coverage of the first dose (between 9 and 10 years old) was 16.1% in 2017 and increased to 50.5% in 2018 (p < 0.0001). The first dose in all ages increased 78% in 2018 compared with 2017 (6,636/3,733). Competing demands over the program continued in 2019, and the first dose coverage dropped (26.9%). For 2020, a municipal law instituted school-based vaccination and the creation of dedicated teams for vaccination, and these strategies are waiting to be tested. Conclusion School-based annual HPV vaccination in children between 9 and 10 years old was feasible and increased vaccination coverage, regardless of gender, although the program was vulnerable to competing events.