School Of Basic And Applied Sciences
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Item A study of mechanistic mapping of novel SNPs to male breast cancer(Humana Press Inc., 2019) Kaur, R.P; Kumar, V; Shafi, G; Vashistha, R; Kulharia, Mahesh; Munshi, AanjanAlterations in BRCA2, PALB2, CHEK2, and p53 genes have been identified for their association with male breast cancer in various studies. The incidence of male breast cancer in India is consistent with its global rate. The present study was carried out with an aim to evaluate the genetic alterations in male breast cancer patients from Malwa region of Punjab, India. Four male breast cancer patients belonging to different families were recruited from Guru Gobind Singh Medical College and Hospital, Faridkot, India. A total of 51 genes reported with implications in the pathogenesis of breast cancer were screened using next generation sequencing. Germline variations were found in BRCA1, BRCA2, PMS2, p53, and PALB2 genes, previously reported to be associated with MBC as well as FBC. In addition to these, 13 novel missense alterations were detected in eight genes including STK11, FZR1, PALB2, BRCA2, NF2, BAP1, BARD1, and CHEK2. Impact of these missense alterations on structure and function of protein was also analyzed through molecular dynamics simulation. Structural analysis of these single nucleotide polymorphisms (SNPs) revealed significant impact on the encoded protein functioning. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.Item Dipropargyl substituted diphenylpyrimidines as dual inhibitors of monoamine oxidase and acetylcholinesterase(Elsevier, 2019) Kumar, Bhupinder; Kumar, V; Prashar, V; Saini, S; Dwivedi, A.R; Bajaj, B; Mehta, D; Parkash, Jyoti; Kumar, VinodAlzheimer's disease (AD) is a multifactorial neurological disorder involving complex pathogenesis. Single target directed drugs proved ineffective and since last few years' different pharmacological strategies including multi-targeting agents are being explored for the effective drug development for AD. A total of 19 dipropargyl substituted diphenylpyrimidines have been synthesized and evaluated for the monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibition potential. All the compounds were found to be selective and reversible inhibitors of MAO-B isoform. These compounds also displayed good AChE inhibition potential with IC50 values in low micromolar range. AVB4 was found to be the most potent MAO-B inhibitor with IC50 value of 1.49 ± 0.09 μM and AVB1 was found to be the most potent AChE inhibitor with IC50 value of 1.35 ± 0.03 μM. In the ROS protection inhibition studies, AVB1 and AVB4 displayed weak but interesting activity in SH-SY5Y cells. In the cytotoxicity studies involving SH-SY5Y cells, both AVB1 and AVB4 were found to be non-toxic to the tissue cells. In the molecular dynamic simulation studies of 30 ns, the potent compounds were found to be quite stable in the active site of MAO-B and AChE. The results suggested that AVB1 and AVB4 are promising dual inhibitors and have the potential to be developed as anti-Alzheimer's drug. © 2019