Designing, molecular docking, and dynamics simulations studies of 1,2,3-triazole clamped Uracil-Coumarin hybrids against EGFR tyrosine kinase

Since the last decade, hybrid drug strategies have attracted many researchers for their improved anti-cancer potential incomparison to single drug components. Complying to this approach, 28 novel Uracil–Coumarin hybrids with differentsized linkers (2–5 carbon atoms) and substituents were designed to occupy the active site of protein epidermal growthfactor receptor (EGFR) tyrosine kinase (Protein Data Bank ID: 1M17). Molecular docking studies were performedfor all ligands (A1-D7) to identify the potential candidate using Schrödinger software. The relative binding affinity ofhybrids toward EGFR was compared with standard Erlotinib on the basis of gScore and Emodel score. Positively, allthe hybrids docked inside the cavity and showed significant interactions, compounds A6, A2, and A7 with short-chainlinker (two carbon atoms) and halogen substituents were found to have more interactions and better docking score thanstandard Erlotinib. The visualization results depicted that compound A6 showed the highest affinity and formed thebest binding pose to the target EGFR with gScore = −8.891 kcal/mol and Emodel score = −100.744 in comparison tostandard Erlotinib (gScore of −8.538 kcal/mol and Emodel score = −80.588). Moreover, a molecular dynamics studyalso reveals that ligand A6 forms a stable complex with root mean square deviation (RMSD) of 0.3 nm and the plateauphase started just after 10 ns (time). Hence, the present research provides computational insights of Uracil–Coumarinhybrids as potential ligands against EGFR tyrosine kinase and in future in vitro investigations of these hybrids mayprove their therapeutic potential against cancer.

Recent advancements in Uracil and 5-Fluorouracil hybrids as potential anticancer agents: A review

Cancer is the most dreadful disease and the second main cause of death worldwide. The continuous developments havebeen going on in order to design potent molecules such that this leading cause of death can be dealt with. In order todecrease the level of toxicity and to improve the selectivity of drugs toward cancer targets, the development of hybridmolecules has become the center of research, and scientists are doing timeless efforts to generate such a hybrid whichhas got no comparison with the previous developments. The heterocyclic moiety Uracil and many of its derivativeswere already exposed as promising anticancer agents. Moreover, coupling of Uracil and 5-Fluorouracil (5-FU) withdifferent pharmacophores has been proven to be an excellent strategy against cancer. Hence, the present review is aneffort to collectively represent all the earlier and recent developments of Uracil and 5-FU hybrids reported to have asignificant anticancer profile. Expectantly, we can assure that this article can serve as the basis for further developmentsin Uracil and 5-FU hybrids and will surely motivate the medicinal chemists for producing unique anticancer drug

Serological, Isolation and Molecular Studies on Brucellosis in an Organized Farm, Jammu and Kashmir, India

The present study was conducted in an organized farm of Jammu region, Jammu and Kashmir state having history of late-term abortions in cattle and buffaloes to elucidate the role of brucellosis in causing abortions on the farm. The farm had 46 animals (23 adults, 15 heifers and 9 calves). The farm was positive in herd test (milk ring test). Serological tests viz., Rose Bengal plate test (RBPT) and serum agglutination test (SAT) were conducted on 30 serum samples and 11 samples were found positive in both tests. Five vaginal swabs from abortion cases were processed for isolation and 3 isolates of Brucella were obtained which on further characterization by biochemical tests, genus-specific PCR and species-specific PCR were identified as B. abortus biovar 1. As brucellosis is an anthropozoonoses, the high prevalence of brucellosis in livestock of farm demands the surveillance of disease in humans working on the farm and necessitates the control of disease on the farm.

Blood Urea & Salivary Urea levels in End Stage Renal Failure.

Elevation of Blood Urea Nitrogen in renal diseases results concomitant increase in Salivary Urea levels. Aims : Determine if there was any correlation between the Salivary Urea levels with that of Blood Urea levels. Material & Methods : samples of blood and saliva were taken from Hemodialysis and control groups to assess the Blood Urea Nitrogen (BUN) and Salivary Urea (SU) levels respectively under strict aseptic precautions. Informed consent was taken from patients and ethical committee approval taken. Results : showed no statistically significant difference between Blood Urea and Salivary Urea in the Hemodialysis group (p>0.05). There was a statistically significant difference between Hemodialysis group and Control group with respect to Blood Urea and Salivary Urea levels. (p<0.001). Conclusion : saliva can be used as a noninvasive diagnostic marker tool.

Evaluation of the relative efficacy of an alloplast used alone and in conjunction with an osteoclast inhibitor in the treatment of human periodontal infrabony defects: A clinical and radiological study.

Background: Mucoperiosteal flap surgery stimulates varying amounts of alveolar bone loss due to accelerated osteoclastic activity [Regional Accelerated Phenomenon (RAP)]. Alendronate sodium inhibits osteoclastic activity and is thought to result in a net increase in osteoblastic activity. We undertook a preliminary study evaluating the effect of adjunctive use of topically delivered bisphosphonate alendronate (ALN) along with regenerative bone graft material in the treatment of periodontal infrabony defects. Materials and Methods: Fifteen patients with two-walled or three-walled infrabony defects were selected. In each patient, the infrabony defect of one side of arch was designated as group A (control site) and received hydroxyapatite (HA) bone graft material, while the infrabony defect on the contralateral side of same arch was designated as group B (test site) and received HA + 200 μg drug solution of ALN. Results: Both the groups exhibited a highly significant reduction in probing depth and gain in clinical attachment level and linear bone fill at the end of 24 weeks. Comparative evaluation between the study groups revealed a statistically nonsignificant reduction in probing depth (P=0.128 NS ) and mean gain in attachment level (P=0.218 NS ). However, there was a statistically significant gain in linear bone fill (P=0.040*) in group B as compared to group A. Conclusions: The results suggest that use of ALN along with graft material led to enhanced linear bone fill at the surgical site. This research provides a clue that bone-targeting properties of bisphosphonates can be harnessed along with regenerative materials to potentiate osseous regeneration.

Comparative study between cervical vertebrae and hand-wrist maturation for the assessment of skeletal age / Estudo comparativo entre maturação de vértebras cervicais e da mão e punho para a determinação da idade esqueletal

Objectives: The aim of the study was to compare the cervical vertebrae maturity, using a lateral cephalogram,which is routinely taken before orthodontic treatment and is included as a part of the patient’srecord, with hand-wrist maturation method. Materials and methods: The study group comprised ofsixty subjects of Bangalore, Indian, origin, aged between 9-18 years. Hand wrist radiograph and lateralcephalograms were taken for these subjects. Assessment of skeletal maturation was done using SkeletalMaturity Indicators (SMI’s) from hand-wrist radiograph and Cervical Vertebrae Maturity Indicators(CVMI’s) from lateral cephalogram. A pair wise comparison for skeletal age assessment stages was doneusing Wilcoxon sign rank test and proportions was compared using Chi-Square test for statistical analysis.Results: Skeletal maturity assessed using the cervical vertebrae maturation index (CVMI) method andhand-wrist skeletal maturational index (SMI) method showed no statistical signifi cant difference for malesand females. However, females showed maturation at an early age as compared to males. Conclusions:Since properly utilized cervical vertebrae assessment provided a reliable assessment of pubertal growthspurt, it would be benefi cial to use a lateral cephalogram for skeletal maturity assessment and thereby eliminate the need for an additional radiograph (hand-wrist radiograph). This is cost effective and will alsoreduce the radiation exposure to the patient.

Objetivos: O objetivo do presente estudo foi comparar a maturidade das vértebras cervicais, por meio de umcefalograma lateral, que é rotineiramente obtido antes de tratamentos ortodônticos, com um método de medição dematuração de mão e punho. Materiais e métodos: O grupo estudado consistiu de sessenta indivíduos da região deBangalore, Índia, com idades entre 9 e 18 anos, de ambos os sexos. Radiografi as de mão e punho e cefalogramas emnorma lateral foram obtidos. A determinação da maturação esquelética foi determinada com o uso de Indicadoresde Maturidade Esquelética para radiografi as de mão e punho e Indicadores de Maturidade de Vértebras Cervicaispara cefalogramas em norma lateral. A comparação por pareamento para determinação da idade esqueletal foi feitautilizando o teste de ranqueamento de Wilcoxon e as proporções comparadas pelo teste Qui-Quadrado para análiseestatística. Resultados: A maturidade esquelética determinada pelo índice de maturação esquelética não mostroudiferença estatística signifi cante para homens e mulheres. Entretanto, em mulheres a maturação ocorreu em idademais precoce quando comparadas com os homens. Conclusões: Uma vez utilizado adequadamente, o método dedeterminação da maturidade das vértebras cervicais proporciona um indicativo confi ável do crescimento no estirãoda puberdade, o qual pode ser útil no estabelecimento da maturidade esqueletal por meio de cefalogramas laterais,eliminando assim a necessidade de radiografi as adicionais de mão e punho. Essa eliminação das radiografi as de mãoe punho é custo-efetiva e igualmente reduz a exposição do paciente à radiação ionizante.

Quassinoids

Quassinoids, the bitter principles isolated from the Simaroubaceous plants, are C-20 oxygenated compounds. Some quassinoids have shown promising antitumour, antiviral, antimalarial, amoebicidal, antileikaemic and antifeedant properties. About 100 quassinoids have been reported in the literature. A comprehensive list of quassinoids containing structural formulae, physical constants, UV, IR, 1H NMR, 13C NMR, EI mass spectral data, semi-synthetic analogues and natural sources have been presented to compare the data of the newly isolated compounds with the reported ones