Computational and Biological Investigations on Abl1 Tyrosine Kinase: A Review.

Abl1 tyrosine kinase is a validated target for the treatment of chronic myeloid leukemia. It is a form of cancer that is difficult to treat and much research is being done to identify new molecular entities and to tackle drug resistance issues. In recent years, drug resistance of Abl1 tyrosine kinase has become a major healthcare concern. Second and third-generation TKI reported better responses against the resistant forms; still they had no impact on long-term survival prolongation. New compounds derived from natural products and organic small molecule inhibitors can lay the foundation for better clinical therapies in the future. Computational methods, experimental and biological studies can help us understand the mechanism of drug resistance and identify novel molecule inhibitors. ADMET parameters analysis of reported drugs and novel small molecule inhibitors can also provide valuable insights. In this review, available therapies, point mutations, structure-activity relationship and ADMET parameters of reported series of Abl1 tyrosine kinase inhibitors and drugs are summarised. We summarise in detail recent computational and molecular biology studies that focus on designing drug molecules, investigation of natural product compounds and organic new chemical entities. Current ongoing research suggests that selective targeting of Abl1 tyrosine kinase at the molecular level to combat drug resistance in chronic myeloid leukemia is promising.

Influence of bacterial strains on Oryza sativa grown under arsenic tainted soil: Accumulation and detoxification response.

The present study was conducted to study the role of bacterial inoculants in growth, accumulation and tolerance responses in rice grown in arsenic (As) contaminated soil. Results revealed that out of five isolated bacterial strains, strain BBAU/MMM1 (Babasaheb Bhimrao Ambedkar University/Mari Matamandir) exhibited resistant to As(III) to the level of 400 µM As(III) in comparison to other strain which showed toxicity. The isolated strain BBAU/MMM1 1was characterized as gram negative, rod shape, showed positive test nitrate, citrate, catalase and phosphate solubilization with high production of IAA and siderophore. Arsenic treated rice seedlings supplemented with bacterial inoculants BBAU/MMM1 showed increased growth characteristics viz., root length (35.41%), shoot length (32.8%) and fresh weight (30.31%) in comparison to rice treated with As(III) only. In addition, reduced lipid peroxidation and induces cysteine, GSH (reduced glutathione), GSSG (Oxidized glutathione) and antioxidant enzymatic activities were also observed in bacterial supplemented rice seedlings. Further, reduced metal accumulation in root (1351.46-968.67 µg g-1fw), shoot (488.01-378.02 µg g-1fw) and reduced translocation factor (0.583-0.390) in As(III) treated rice seedlings inoculated with bacterial strains clearly reflect protective response of bacterial strain against As toxicity. Thus, isolated bacterial strain could be used as bioremediator as well as growth inducer in paddy field contaminated with arsenic.

Antimicrobial resistance among enteric bacteria, isolated from runoff of the Gangotri glacier, western Himalaya India.

An attempt has been made to study antimicrobial resistance among the coliforms, faecal coliforms and faecal streptococci isolated from the runoff of the Gangotri glacier. The number of multiple antibiotic resistances (MAR) coliform isolates increases from upper stretch (33.33%) to lower stretch (83.33%). All faecal coliforms (100%) and faecal streptococci (100%) of lower stretch of study area showed multiple antibiotic resistances. Among coliforms, the value of Antibiotic resistance index (ARI) was found maximum in lower stretch (0.34) followed by middle stretch (0.29) and upper stretch (0.25).