Novel applications of atomic softness and QSAR study of testosterone derivatives

Abstract

Testosterone is an important steroidal hormone. The parent scaffold consists of 19 carbon atoms and acts via androgen receptor-directly or as 5a-dihydrotestosterone (DHT)-or by conversion into estradiol and activation of certain estrogen receptors. In silico assessment of activity towards their receptor was performed using quantum-chemical descriptors. Various essential indices were calculated using semiempirical parameterized model 3 (PM3) calculations. The descriptors values were statistically correlated using multiple linear regression analysis. Quantitative structure-activity relationship (QSAR) study indicated that the acidic properties of these derivatives have significant relationships with observed biological activity. Global acidic nature as well as atomic acidic character showed key interaction with the receptor. This study might be helpful to describe further ligands with improved activity.

Update 2 of: Electrophilicity Index

“…Experimental toxicity values (pIC 50 ) of a variety of polyaromatic hydrocarbons 398 such as PCDFs, PCDDs, and polychlorinated biphenyls (PCBs) as well as those of several aliphatic amines 397 correlate well with the corresponding toxicity values calculated using the HF energy along with the global and local electrophilicities. Electrophilicity index has also been made use of in analyzing antitumoral activity of synthetic chalcones, 399 cisplatinum complexes, 400,401 testosterone derivatives, 402 synaptosomal toxicity of 4-hydroxyl-2-nonenal, 403 toxicity of PCDDs, 404 hemolytic activity of methacrylates, 405 activation of AhR by some biphenyls, 406 metal-binding specificity of porphyrins, 407 effect of plant growth regulators on chloroacetanilide herbicides, 408 reactivity of porphyrin pincers, 409 mutagenic activity of dinitrobenzo[a]pyrene isomers, 410 activities of nonbenzodiazepine compounds, 411 radicalscavenging activity of flavones, 412 cancer-cell membrane lysis properties of peptides like PNC-27, 413 different sulfonamides as carbonic anhydrase inhibitors against isozyme, CA-II, 414 skin sensitization potential of alkenes, 415,416 arsenic toxicity, 417 toxicity of electrophilic sugars, 418 pyridodiindoles, 419 etc. Biological activities of N-phenyl benzamides (antimicrobial agents) 420 and nifurtimox analogues (antiparasitic agents) 421 are also correlated with electrophilicity and its local variants.…”

Drug-Receptor Interaction of Peptidic HIV-1 Protease: Polar Effect-II

“…The values of various parameters to solve modified Klopman softness have been calculated by softness calculator which was developed by Singh research group [4]. Singh et al made Klopman equations applicable for neutral Lewis acids (transition metal salts) and bases (organic molecules) and also extended its application to biological systems for site selectivity and to explain reaction mechanism (markovnikov and anti-markovnikov rule), ligand-receptor interaction of testosterones, estrogens and tetrahydroimidazobenzodiazepinone [19][20][21][22][23].…”

A DFT Study on Estrone – TNT Interaction

“…The carcinogenic activities of estrone and estradiol were investigated by DFT method 2. Quantitative Structure Activity Relationship (QSAR) studies (QSAR: the method that is used to find out the relationship between the biological activities and quantum chemical properties of the molecules) of different sets of hormone molecules containing estrone were published 7–10. Additionally, the structural and electronic properties and oxidation reactions of estrogen hormones including estrone were studied using DFT method 11…”