Investigating the Impact of Different Acrylamide (Electrophilic Warhead) on Osimertinib’s Pharmacological Spectrum by Molecular Mechanic and Quantum Mechanic Approach

Background: Lung cancer has become the prominent cause of the cancer-related deaths globally. More than 80 % of all lung cancers have been diagnosed with Non- Small Cell Lung Cancer (NSCLC). The USFDA approved osimertinib to treat patients with metastatic T790M EGFR NSCLC on a regular basis in March 2017. Recently, C797S mutation to osimertinib has been reported, which indicates the need for structural modification to overcome the problem of mutation. Objective: In this bioinformatics study, we have evaluated the impact of various acrylamide as an electrophilic warhead on the activity and selectivity of osimertinib. Result: Osimertinib analouge 48, 50, 60, 61, 67, 75, 80, 86, 89, 92, 93, 116 and 124 were the most active and selective compounds against T790M EGFR mutants compared to Osimertinib. Conclusion: These compounds also showed less inclination towards WT-EGFR.

Ancestral Veda Concepts and Quantum Mechanic as a background of Ayurveda and Modern Medicine

Ayurveda deals with the relationship between communications and forces to be present either in the human beings or in their environment, including the influence either from their family or social and cultural processes. The exchange between man and nature or environment is a whole and dynamic balance. The outcome of this single or unique dialogue can be more or less harmonious; so that the consequence will determine health status: balanced or imbalanced. This relationship of Communication and Integrated Intelligence plays its role in the microcosm, by the way, in the person itself. In Addition it is being inserted into the world or macrocosm, and it isnamed awareness. I want to quote some examples of this reality that is, actually, unavoidable. In fact, it can not be excluded from the philosophical and practical principles of medicine.

A new approach to understanding structure, functions and classificasion of GABA-benzodiazepine receptor complex, a molecular target for creation of new anticonvulsants on the base of inhibitory amino acids

The GABA molecule was shown to the methods of quantum mechanic characteristics and molecular geometry has three conformational states: linear (GABA-1 conformer), cyclic (GABA-2 comformer) and bucket-like (GABA-3 conformer). The play different functions in the brain neurons: cyclic and bucket-like conformers play role of endogenous transmitters, and linear conformer participates in neuronal metabolism. The theoretical conformational analysis shows there are two types of GABA receptors in the CNS neurons: GABA-2 receptors, agonists of which are cyclic conformer of GABA, glycine and β-alanine and antagonists are bemegride, pentilentetrazol and strychnine; and GABA-3 receptors, agonists of which is bucket-like conformer of GABA and antagonists are picrotoxin and bicuculline. Anticonvulsive and other behavioral effects of derivatives of barbituric acid, benzazepine, benzodiazepine, gidantoine, succinimide and oxasolidindione are realized probably via GABA-2 receptors to switch on them the following functional centers of their structure are nessesary: α, γ and [δ-ε] for barbitirates; β, [δ-ε] and γ for carbamazepine; β and [δ-ε] for benzodiazepine derivatives, gabapentine and vigabatrine; α, β, γ and [δ-ε] for gidantoine and oxasolidindione derivatives; α, β, γ for succinimide derivatives. The power of any behavioral effect of anticonvulsants and inhibitory amino acids depends on power, location and numbers of hydrogen bounds developed between active centers of pharmacophore of anticonvulsant or inhibitory amino acids and active centers of functional skeleton of GABA-2 receptor complex, these properties determine absense of nootropic activity in anticonvulsive drugs and presense of them in inhibitory amino acids. It is concluded there are perspectives of synthesis of conpounds, pharmacophore of which should be like as cyclic conformer of GABA, glycine and β-alanine on their quantum mechanic characteristics and molecular geometry

Coarse graining of force fields for metal–organic frameworks

We have adapted our genetic algorithm based optimization approach, originally developed to generate force field parameters from quantum mechanic reference data, to derive a first coarse grained force field for a MOF, taking the atomistic MOF-FF as a reference.

A combined molecular dynamic and quantum mechanic study of the solvent and guest molecule effect on the stability and length of heterocyclic peptide nanotubes

Guest molecules and solvents affect the stability and length of the heterocyclic peptide nanotube through the electrostatic interactions.