In-vitro and in-silico analysis and antitumor studies of novel Cu(II) and V(V) complexes of N-p-Tolylbenzohydroxamic acid.

Copper(L2Cu) and vanadium(L2VOCl) complexes of N-p-tolylbenzohydroxamic acid (LH) ligand have been investigated for DNA binding efficacy by multiple analytical, spectral, and computational techniques. The results revealed that complexes as groove binders as evidenced by UV absorption. Fluorescence studies including displacement assay using classical intercalator ethidium bromide as fluorescent probe also confirmed as groove binders. The viscometric analysis too supports the inferences as strong groove binders for both the complexes. Molecular docking too exposed DNA as a target to the complexes which precisely binds L2Cu, in the minor groove region while L2VOCl in major groove region. Molecular dynamic simulation performed on L2Cu complex revealing the interaction of complex with DNA within 20 ns time. The complex stacked into the nitrogen bases of oligonucleotides and the bonding features were intrinsically preserved for longer simulation times. In-vitro cytotoxicity study was undertaken employing MTT assay against the breast cancer cell line (MCF-7). Potential cytotoxic activities were observed for L2Cu and L2VOCl complexes with IC50 values of showing 71 % and 74 % of inhibition respectively.

Comorbidities in Paediatric Psoriasis: Experience from a Tertiary Care Centre.

Background: Psoriasis begins in childhood in around one-third of the cases. There has been conflicting evidence regarding the association of paediatric psoriasis with comorbidities. Aims and Objectives: The objective of this study was to find out various comorbidities (abnormal body mass index, metabolic syndrome, lipid abnormalities, diabetes mellitus, and raised blood glucose) associated with paediatric psoriasis. Materials and Methods: All patients of psoriasis (age <18 years) who visited the Paediatric Psoriasis clinic from January 2017 to September 2021 were recruited in this record-based study. Results: Records of 100 patients were analysed, with female to male ratio of 1:1. The age group ranged from 11 months to 18 years. The average body surface area involved was 5.43%. The average psoriasis area and severity index was 2.47. Joint involvement was seen in 7% of patients in our study. A total of 52 (52%) patients had abnormal body mass index, out of which 21 patients were overweight and 31 were obese. At least one lipid abnormality was found in 66 (66%) patients. The most common lipid abnormality was decreased high-density lipoprotein, followed by raised total cholesterol, raised total triglycerides and raised low-density lipoprotein. 8 (8%) patients were found to have raised blood glucose levels. Out of which, six had impaired fasting glucose and two were diagnosed with diabetes mellitus. 5 (5%) patients were diagnosed with metabolic syndrome. Conclusion: Paediatric psoriasis is a chronic disfiguring disease and may have profound emotional and psychological effects. There is a lack of studies from India on the prevalence of these comorbidities in paediatric psoriasis. More studies are required from different parts of the world for a better understanding of paediatric psoriasis.

Interaction of cobalt(II) and copper(II) hydroxamates with polyriboadenylic acid: An insight into RNA based drug designing.

The polyadenylic acid [poly(A)] tail of mRNA plays a noteworthy role in the initiation of the translation, maturation, and stability of mRNA. It also significantly contributes to the production of alternate proteins in eukaryotic cells. Hence, it has recently been recognized as a prospective drug target. Binding affinity of bis(N-p-tolylbenzohydroxamato)Cobalt(II), [N-p-TBHA-Co(II)] (1) and bis(N-p-naphthylbenzohydroxamato)Copper(II), [N-p-NBHA-Cu(II)] (2) complexes with poly(A) have been investigated by biophysical techniques namely, absorption spectroscopy, fluorescence spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy, circular dichroism spectroscopy, viscometric measurements and through molecular docking studies. The intrinsic binding constants (Kb) of complexes were determined following the order of N-p-TBHA-Co(II)] > N-p-NBHA-Cu(II), along with hyperchromism and a bathochromic shift for both complexes. The fluorescence quenching method revealed an interaction between poly(A)-N-p-TBHA-Co(II)/poly(A)-N-p-NBHA-Cu(II). The mode of binding was also determined via the fluorescence ferrocyanide quenching method. The increase in the viscosity of poly(A) that occurred from increasing the concentration of the N-p-TBHA-Co(II)/N-p-NBHA-Cu(II) complex was scrutinized. The characteristics of the interaction site of poly(A) with N-p-TBHA-Co(II)/N-p-NBHA-Cu(II) were adenine and phosphate groups, as revealed by DRS-FTIR spectroscopy. Based on these observations, a partial intercalative mode of the binding of poly(A) has been proposed for both complexes. Circular dichroism confirmed the interaction of both the complexes with poly(A). The molecular docking results illustrated that complexes strongly interact with poly(A) via the relative binding energies of the docked structure as -259.39eV and -226.30eV for N-p-TBHA-Co(II) and N-p-NBHA-Cu(II) respectively. Moreover, the binding affinity of N-p-TBHA-Co(II) is higher in all aspects than N-p-NBHA-Cu(II) for poly(A).