Computer Automated Structure Evaluation (CASE) of the teratogenicity of retinoids with the aid of a novel geometry index

Abstract

The CASE (Computer Automated Structure Evaluation) program, with the aid of a geometry index for discriminating cis and trans isomers, has been used to study a set of retinoids tested for teratogenicity in hamsters. CASE identified 8 fragments, the most important representing the non-polar terminus of a retinoid with an additional ring system which introduces some rigidity in the side chain. The geometry index helped to identify relevant fragments with an all-trans configuration and to distinguish them from irrelevant fragments with other configurations.

An International Comparison of Teratogen Consultation Systems (Motherisk and Toranomon) and a Proposed Optimal System with an Innovative Risk Calculation Formula

“…To determine whether any teratogen computer system similiar to the Motherisk system existed, the DIALOG Medline search was conducted by using three key words: "teratogen," "system," and "computer." Eleven articles were retrieved, however, none of them appeared to be as good as the Motherisk system (17)(18)(19)(20)(21)(22)(23). The Toranomon consultation system created a new risk-evaluation formula.…”

Exhaustive enumeration of molecular substructures

“…As an objective method that can be uniformly applied to essentially all the scaffolds of interest in combinatorial chemistry, the calculation of total and unique fragment counts could provide indices for ''molecular diversity.'' Such analyses and the comparison of fragment distributions from different sets of molecules with related behaviors may lead to the deduction of the statistically important fragments, in the spirit of the work carried out in areas of toxicology 5,7 and environmental hazards. In essence, this approach may be developed into a means to identify moieties whose abundance suggests importance of function and which might be responsible for a given activity.…”

“…The 75 isomers of decane were ranked according to the length of the longest chain of atoms present in each. The numbers of isomers with longest chains of length 10,9,8,7,6, and 5 are, respectively: 1, 4, Ž . 13, 26, 22, and 9.…”

“…2 ''retrosynthetic analysis'' , NMR spectra prediction, 3 calculation of partition coefficients, 4,5 and elucidation of fragmentation mechanisms in mass spectrometry. 6 In biological applications, analysis of molecular fragments has proven extremely useful in, for example, the computer-aided evaluation of chemical toxicity 7,8 and in the search for analogs in chemical databases.…”

Multiple Computer‐Automated structure evaluation program study of aquatic toxicity 1: Guppy

“…This program has been described previously [23,24] and has been used to create predictive models for the activity of structurally diverse chemicals in a number of different biological phenomena. The approach has been used to predict antimycobacterial activity [25], capsaicin's antiinflammatory activity [26], and reversal of multidrug resistance in cancer therapy [27] as well as to uncover attributes of activity in carcinogenicity [28], mutagenicity [29], teratogenicity [30], and other toxic biological endpoints. The program has also been used to create models for such physicochemical properties as pKa, log Kow, and water solubility [23,24].…”