One-pot multicomponent synthesis of novel pyridine derivatives for antidiabetic and antiproliferative activities.

Background: Due to the close relationship of diabetes with hypertension reported in various research, a set of pyridine derivatives with US FDA-approved drug cores were designed and integrated by artificial intelligence. Methods: Novel pyridines were designed and synthesized. Compounds MNS-1-MNS-4 were evaluated for their structure and were screened for their in vitro antidiabetic (α-amylase) activity and anticancer (HepG2) activity by methyl thiazolyl tetrazolium assay. Comparative 3D quantitative structure-activity relationship analysis and pharmacophore generation were carried out. Results: The study revealed MNS-1 and MNS-4 as good alternatives to acarbose as antidiabetic agents, and MNS-2 as a more viable, better alternative to doxorubicin in the methyl thiazolyl tetrazolium assay. Conclusion: This combination of studies identifies new and more active analogs of existing FDA-approved drugs for the treatment of diabetes.

Association of genotypes at rs438228855 in bovine SLC35A3 receptor gene of Pakistani cattle with the susceptibility to develop complex vertebral malformation.

The aim of this study was to report the genotype and allelic frequency at rs438228855 (G > T) in SLC35A3 receptor gene and its association with a complex vertebral malformation (CMV) in the enrolled Pakistani cattle. Our results indicated that allelic and genotype frequency at rs438228855 varied non-significantly (p > .05) among the three enrolled cattle breeds. GT (heterozygous) genotype was most abundant (0.54) followed by GG (wild type) genotype (0.45) while the mutant genotype (TT) was not observed among the enrolled cattle. It was observed that the Holstein Friesian breed had more GG (wild) than GT (heterozygous) genotypes while Sahiwal and cross cattle breed had more heterozygous (GT) combination at rs438228855 than the wild (GG) genotype. Significant variations in white blood cell count, % lymphocytes, red blood cell count, % monocytes, haemoglobin, mean corpuscular volume and mean corpuscular haemoglobin concentration were observed when compared between the enrolled cattle breeds. Most of the studied haematological parameters showed no association with the genotype at rs438228855. In conclusion, the heterozygosity at rs438228855 is not limited to the Holstein Friesian breed as local Sahiwal and crossbred cattle had also higher heterozygosity at rs438228855. We recommend that animals must be genotyped for rs438228855 before their selection as breeders to prevent economic losses.