Molecular Docking and 3D-QSAR Based Design of Novel Imidazopyridinone Derivatives as Pseudomonas Aeruginosa Thymidylate Kinase Inhibitors

Abstract: Thymidylate kinase (TMK) is a potential chemotherapeutic target since it is directly involved in the synthesis of deoxythymidine 5'-triphosphate an essential component in DNA replication. Inhibiting the function of TMK blocks DNA synthesis in replicating organisms. We report 3D-QSAR analysis on a series of thymidine mimetics exhibiting potent inhibitory activity against TMK. Molecular docking, Comparative molecular field analysis (CoMFA) and comparative similarity indices analysis (CoMSIA) were carried out to determine the requisite 3D structural features required for potent thymidylate kinase inhibitory activity. The molecules were divided into training set and test set, a PLS analysis was performed and QSAR models were generated. The model showed good statistical reliability which is evident from the q 2 loo , r 2 ncv and r 2 pred . The models were graphically interpreted using CoMFA and CoMSIA contour maps. The results obtained from this study were used for rational design of potent inhibitors against thymidylate kinase

Under the supervision of

All sentences or passages quoted in this dissertation from other people's work have been specifically acknowledged by clear cross-referencing to author, work and page(s). Any illustrations which are not the work of the author of this dissertation have been used with the explicit permission of the originator and are specifically acknowledged. I understand that failure to do this amounts to plagiarism and will be considered grounds for failure in this dissertation and the degree examination as a whole

Severity of Peri-ictal Respiratory Dysfunction With Epilepsy Duration and Patient Age at Epilepsy Onset.

Respiratory dysfunction preceding death is fundamental in sudden unexpected death in epilepsy (SUDEP) pathophysiology. Hypoxia occurs with one-third of seizures. In temporal lobe epilepsy, there is volume loss in brainstem regions involved in autonomic control and increasing neuropathological changes with duration of epilepsy suggesting increasingly impaired regulation of ventilation. In animal models, recurrent hypoxic episodes induce long-term facilitation (LTF) of ventilatory function, however, LTF is less robust in older animals. LTF of ventilation may, to some degree, ameliorate the deleterious effects of progressive brainstem atrophy. We investigated the possibility that the duration of epilepsy, or age at epilepsy onset, may impact the severity of seizure-associated respiratory dysfunction. Patients with focal epilepsy undergoing video-EEG telemetry in the epilepsy monitoring unit (EMU) were studied. We found a significant relationship between age at epilepsy onset and duration of peri-ictal oxygen desaturation for focal seizures not progressing to bilateral tonic-clonic seizures, with longer duration of peri-ictal oxygen desaturation in patients with epilepsy onset at an older age but no significant relationships between duration of epilepsy or age at EMU admission and ventilatory dysfunction. Our findings suggest an intriguing possibility that LTF of ventilation may be protective when epilepsy starts at a younger age

A clinico-epidemiological study of facial dermatoses in women

Background: The face is the most prominent part of the body. Facial blemishes and disorders directly reflect on patients' physical appearance, cosmesis, and self-image. They may contribute to dysmorphism and even lead to depressive illness in susceptible individuals, especially women. Therefore, it is essential for the early identification and management of facial skin disorders. Aims: To study the clinical pattern and epidemiological determinants of facial dermatoses among females above ten years. Materials and Methods:This cross-sectional study was conducted in a rural tertiary hospital from January 2019 to December 2019 among 500 female patients with Facial Dermatoses with their consent. Investigations, including the skin scrapings for potassium hydroxide mount, woods lamp examination, skin biopsy, and relevant investigations, wherever required, were done. Females above the age of 10 years with facial dermatoses were included with due consent/ assent. Patients with drug reactions and sexually transmitted infections (STIs) were excluded. Results: Out of the total 500 cases enrolled, most were in the 4th (22%) and fifth (19%) decades. Patients with only one facial dermatosis were 321 (64.2%), whereas 179(35.8%) patients had more than one dermatoses. Among the facial dermatoses, pigmentary dermatoses were highest 355 (71%), with melasma predominating. The least common were immunobullous dermatoses 5 (1%). In the study, many facial dermatoses, especially melasma, were related to occupation and lifestyle with the patients giving a history of photo-aggravation, stress, and cosmetics use. Occupation-wise, agricultural workers were the major group of 196 (38%), followed by housewives with 154 (30%) out of 500. Conclusion: The subject is complex, as the term facial skin disorder includes a large heterogeneous group of disorders, but no precise classification exists. Opinions vary regarding the conditions to be included under facial dermatoses. This study is an effort to fill this gap in understanding facial dermatoses, which have a significant bearing on physical and mental well-being and the Dermatological Quality of life (DLQI) among the female clientele