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Biomedical subjects

C Hansch

Publications and source records attributed to C Hansch.

At least 127 records · Page 7Linked to original sources
PubMed1979

Structure-activity relationship of aniline mustards acting against B-16 melanoma in mice.

A set of 23 aniline mustards [X-C6H4N(CH2CH2Cl)2] have been tested for their activity against B-16 melanoma in mice. The following quantitative structure-activity relationship (QSAR) correlates the data well: log 1/C = -2.06 sigma - 0.15 pi - 0.13 pi2 + 4.13 (r = 0.936). When this equation is compared with those formulated for aniline mustards acting against leukemia, it is found that log P0 (ideal lipophilicity) is higher for solid tumors. The QSAR brings out the unique activity of phenylalanine aniline mustard.

Aniline Mustard↗
PubMed1979

The interaction of ligands with enzymes. A starting point in drug design.

The problem of inhibiting a specific enzyme of a pathogen without inhibiting the corresponding enzyme of the host is one which has intrigued medicinal chemists for years. While it is easy to find potent inhibitors of purified enzymes transforming these inhibitors into effective drugs, it still is a very poorly understood business. This report discusses studies with two enzymes, papain and dihydrofolate reductase, and the nonspecific (phi and MR correlated) interaction of ligands with them. The QSAR which has been developed for the inhibition of dihydrofolate reductase by triazines is compared with the QSAR which has been reported for the same inhibitors acting against S. aureus.

Animals↗
PubMed1979

QSAR in cancer chemotherapy.

Interest in the formulation of quantitative structure-activity relationships (QSAR) for antitumor drugs has begun to develop in the past decade. The work in this area has been reviewed briefly, using as examples studies on nitrosoureas, aniline mustards, and aryl triazenes. A salient conclusion from this analysis is that the present drugs in clinical use are more hydrophilic than one might expect. The reason for this may be that they have been developed using leukemia as the test system which may in part account for the fact that while the currently used drugs are effective against leukemia, they are not effective in general against solid tumors.

Aniline Mustard↗
PubMed1979

QSAR of alkyl pyridinecarbonyldithiocarbazates as uncouplers of oxidative phosphorylation.

The structure-activity relationship for alkyl dithiocarbazates and alkyl pyridinecarbonyldithiocarbazates as oncouplers of oxidative phosphorylation in rat liver mitochondria has been studied using subsituent constants and regression analysis. As in various other uncouplers, the hydrophobic property of substituents gave a good correlation with their biological activities. 4-Pyridinecarbonyldithiocarbazates are the most active among the congeners studied.

Animals↗
PubMed1979

QSAR of the inhibition of glyoxalase by S-substituted glutathiones.

A quantitative structure-activity relationship (QSAR) has been formulated for the inhibition of glyoxalase I from yeast by 37 S-substituted glutathiones: log 1/C = 1.23 pi' + 1.20 MR4 - 0.67 I1 - 0.14 pi'2 + 1.85 C in this expression is the molar concentration of inhibitor producing 50% inhibition, pi' is the usual hydrophobic parameter modified for certain substituents, MR4 is the molar refractivity of certain p-phenyl substituents, and I1 is an indicator variable for those congeners with an acetylated alpha-amino group. This equation should be of help in the design of more effective inhibitors which may be of value in cancer chemotherapy.

Chemical Phenomena↗
PubMed1978

Structure-activity relationships in antitumor aniline mustards.

Quantitative structure-activity relationships (QSAR) have been formulated for the hydrolysis of aniline mustards and their antitumor activity against Walker 256 tumor and L1210 and P388 leukemia. In general, the antitumor activity parallels hydrolysis under the conditions defined by Ross; toxicity (LD50) parallels antitumor efficacy. Chlorambucil is an exception. A most important finding is that ideal lipophilicity for effectiveness against Walker tumor appears to be much higher than for the leukemias which suggests that solid tumors may, in general, require more lipophilic drugs than leukemias.

Aniline Mustard↗
PubMed1978

Antitumor 1-(X-aryl)-3,3-dialkyltriazenes. 1. Quantitative structure-activity relationships vs. L1210 leukemia in mice.

Quantitative structure-activity relationships (QSAR) have been formulated for phenyl-, pyrazolyl-, and imidazolyltriazenes acting L1210 leukemia in mice. All three sets of congeners have the same ideal lipophilicity (log Po approximately 1). Electron releasing substituents increase potency; ortho substitution decreases activity. The synthesis of a number of new triazenes and some of their partition coefficients are reported.

Animals↗
PubMed1978

Antitumor 1-(X-aryl)-3,3-dialkyltriazenes. 2. On the role of correlation analysis in decision making in drug modification. Toxicity quantitative structure-activity relationships of 1-(X-phenyl)-3,3-dialkyltriazenes in mice.

A series of 11 triazenes (X-C6H4N=NNRCH3) was characterized for toxicity in mice (LD50). The quantitative structure-activity relationship (QSAR) obtained for toxicity was compared with the QSAR for antitumor activity. The close correspondence of the two QSAR leaves essentially no means for the synthesis of more potent, less toxic triazenes.

Animals↗
PubMed1977

Quantitative structure-activity relationships of antimalarial and dihydrofolate reductase inhibition by quinazolines and 5-substituted benzyl-2,4-diaminopyrimidines.

A quantitative structure-activity relationship (QSAR) for the inhibition of dihydrofolate reductase from S. faecium by quinazolines has been formulated. This is compared with a QSAR for inhibition of E. coli dihydrofolate reductase by 2,4-diamino-5-benzylpyrimidines. The QSAR for inhibition of bacterial enzyme is compared with QSAR for mammalian enzyme inhibition. A QSAR has been formulated for the antimalarial action of quinazolines against P. berghei in mice. The antimalarial QSAR is consistent with that of the in vitro bacterial study.

Animals↗
PubMed1977

Substituent constants for correlation analysis.

Constants for pi and omega ahve been measured for a miscellaneous group of aromatic substituents of interest to medicinal chemists. Swain and Lupton's gamma and kappa values have been calculated from the omego constants. Values for molar refractivity are also given for each of the substituents.

Chemical Phenomena↗
PubMed1977

Quantitative structure-activity relationship of chymotrypsin-ligand interactions.

Quantitative structure-activity relationships (QSAR) have been formulated for the interactions of a variety of ligands with chymotrypsin. The parameters Km, k2, k3, kcat, and Ki are found to be strongly dependent on molar refractivity as well as steric and electronic character of the substituents in structures of the type R2CH(COOR3)NHCOR1 where R may be H. A model for binding of D and L esters is presented which gives a consistent view of the binding step, acylation, and deacylation. The model suggests new avenue for exploration.

Acylation↗