Quantitative Structure-Activity Relationships of 1.2.3 Triazole Derivatives as Aromatase Inhibition Activity

Abstract

Aromatase is an estrogen biosynthesis enzyme belonging to the cytochrome P450 family that catalyzes the rate-limiting step of converting androgens to estrogens. As it is pertinent toward tumor cell growth promotion aromatase is a lucrative therapeutic target for breast cancer. In the pursuit of robust aromatase inhibitors, a set of thirty 1-substituted mono-and bis-benzonitrile or phenyl analogs of 1.2.3triazole letrozole were employed in quantitative structure activity relationship (QSAR) study using multiple linear regression (MLR).The results demonstrated good predictive ability for the MLR model. After dividing the dataset into training and test set. The models were statistically robust internally (R 2 = 0.982) and the model predictability was tested by several parameters, including the external criteria (R 2 pred = 0.851. CCC= 0.946). Insights gained from the present study are anticipated to provide pertinent information contributing to the origins of aromatase inhibitory activity and therefore aid in our on-going quest for aromatase inhibitors with robust properties.

Investigation of salicylidene acylhydrazides derivatives: Molecular Docking, ADMET, and Molecular Dynamic Simulations were used in conjunction towards the design of new Yersinia pseudotuberculosis inhibitors

“…Typically, a high solubility goes along with good absorption. Therefore, compound 4,18,20,25,31,36,44, and 57 have their cLogS calculations greater than -4, while all the reference drugs are less than -4 shows low solubility with bad absorption. Molecules showing good absorption or permeation are likely to have hydrogen bond donors (HD) not more than 5 and hydrogen bond acceptors (HA) not more than 10 to enhance the probability of good intestinal permeability.…”

“….85 MW = Molecular weight; HA = hydrogen bond acceptor; HD = hydrogen bond donor; TSA = total surface area; PSA = polar surface area In drug-likeness property, a positive value for the chemicals states that the molecule contains predominantly fragments that are frequently present in commercial drugs [33]. Compounds 20,25,36,41,44, and 49 showed negative values for the druglikeness properties (i.e., they do not contain fragments that are frequently present in market drugs). The toxicity risk values were predicted using the software Data warrior (OSIRIS) are shown as none, low, and high for its mutagenic, tumorigenic, irritant, reproductive effective properties.…”

“…The ligand efficiency (LE) is free binding energy in kcal/mol per nonhydrogen atom or heavy atom calculated from IC50 [35]. A truly good hit or lead compound has LE greater than 0.3 and the results show that all the selected compounds have their LE greater than 0.3 [11,36]. This indicates that the compounds have a desirable LE potency at the right molecular weight.…”

Quantitative Structure Activity Relationship (QSAR) Investigations and Molecular Docking Analysis of Plasmodium Protein Farnesyltransferase Inhibitors as Potent Antimalarial Agents

“…The reliability of a QSAR classification model depends on its capacity to achieve confident predictions of new compounds not considered in the building of the model [29]. The ability of a QSAR classification model to make credible predictions of novel compounds not addressed in the model's construction determines its dependability.…”