Quantitative Structure Inter-Activity Relationship (QSInAR). Cytotoxicity Study of Some Hemisynthetic and Isolated Natural Steroids and Precursors on Human Fibrosarcoma Cells HT1080

Abstract

Combined experimental and quantitative structure inter-activity relationship (QSIAR) computation methods were advanced in order to establish the structural and mechanistic influences that steroids and triterpenes, either as newly synthesized or naturally isolated products, have on human HT1080 mammalian cancer cells. The main Hansch structural indicators such as hydrophobicity (LogP), polarizability (POL) and total energy (Etot) were considered and both the structure-projected as well as globally computed correlations were reported; while the inter-activity correlation of the global activity with those projected on structural information was revealed as equal to the direct structural-activity one for the trial sets of compounds, the prediction for the testing set of molecules reported even superior performances respecting those characteristic for the calibration set, validating therefore the present QSInAR models; accordingly, it follows that the LogP carries the most part of the cytotoxic signal, while POL has little influence on inhibiting tumor growth—A complementary behavior with their earlier known influence on genotoxic carcinogenesis. Regarding the newly hemisynthetic compounds it was found that stigmasta-4,22-dien-3-one is not adapted for cell membrane diffusion; it is recommended that aminocinnamyl chlorohydrate be further modified in order to acquire better steric influence, while aminocinnamyl-2,3,4,6-O-tétraacétyl-α-D-glucopyranoside was identified as being inhibited in the tumor cell by other molecular mechanisms–here not revealed–although it has a moderate-high anti-cancer structurally predicted activity.

Cholesterol Metabolism: A Potential Therapeutic Target in Glioblastoma

“…Steroids and their derivatives or triterpene precursors such as betulinic, oleanolic, and ursolic acids and stigmasterol have shown strong anti-cancerous properties [95,96,97]. Cholesterol derivatives, for example, sodium cholesteryl sulfate, cholesteryl chloride, cholesteryl bromide, and cholesteryl hemi-succinate, have been reported to possess inhibitory activities against DNA polymerase and DNA topoisomerase and to inhibit human cancer cell growth [98].…”

Synthesis of oxygenated oleanolic and ursolic acid derivatives with anti-inflammatory properties

“…10 In more modern work, all four of the above mentioned triterpenes have shown important biological activity, notably against human cancer cells. Maslinic acid inhibited the growth of adenoid, 11 astrocytoma, 12 breast, 13,14 cervical, 12 colon, 15,16 fibrosarcoma, 17 lung, 15 ovarian, 15 and melanoma 13,15 cancer cells. The compound 3- epi -maslinic acid demonstrated activity against gastric and uterine cancer cells.…”

Design, Synthesis, Antifungal Activities and 3D-QSAR of New N,N'-Diacylhydrazines Containing 2,4-Dichlorophenoxy Moiety

“…The classical QSAR methods are 2D-QSAR and 3D-QSAR, because they allow rapid generation of QSARs from which biological activity of newly designed molecules can be predicted. Many QSAR methods had been developed, such as catastrophe QSAR [ 16 ], Alert-QSAR [ 17 ], Quantum-SAR [ 18 ], QSInAR [ 19 ], Hologram QSAR [ 20 ], Residual-QSAR [ 21 ] and so on. Currently, a new 2D-QSAR method, using Simplified Molecular Input Line Entry System (SMILES) molecules [ 22 , 23 ], will provide new insight in unfolding the necessary mechanism picture of a QSAR study in accordance with the Organization for Economic Co-Operation and Development (OECD) criteria[ 24 ].…”