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A K Debnath

Publications and source records attributed to A K Debnath.

24 records · Page 2Linked to original sources
PubMed1989

Mutagenicity of dimethyl heteroaromatic triazenes in the Ames test: the role of hydrophobicity and electronic effects.

The mutagenicities of five heterocyclic 3,3-dimethyltriazenes have been evaluated in the Ames test. The octanol-water partition coefficients (P) for these triazenes have been measured, and their electron distributions and molecular orbital energies were calculated using the MNDO semiempirical molecular orbital method. Molecular structures of three triazenes have been determined using X-ray crystallography. The mutagenicities of these five triazenes, which range from nearly inactive to very highly mutagenic, are well predicted by quantitative structure-activity relationships that had been derived previously for the mutagenicity of aryltriazenes. The form of these equations indicates that more hydrophobic and more electron-rich triazenes are more active in the Ames test. This supports the hypothesis that the ease of initial triazene activation by cytochrome P-450 governs the mutagenicity of these compounds.

Biotransformation↗
PubMedDate not supplied

Blocking of CD4 cell receptors for the human immunodeficiency virus type 1 (HIV-1) by chemically modified bovine milk proteins: potential for AIDS prophylaxis.

The chemical transformation of synthetic combinatorial libraries to increase the diversity of compounds of medicinal interest was reported recently. Chemical modification of natural products represents a complementary approach to accomplish this aim. Modification of lysines by aromatic acid anhydrides, preferentially by 3-hydroxyphthalic and trimellitic anhydrides and trimellitic anhydride chloride, converted commonly available proteins (human and bovine serum albumin and casein) into potent inhibitors of (i) binding between the HIV-1 gp 120 envelope glycoprotein and the CD4 cell receptor, probably owing to their binding to CD4, and (ii) infection by HIV-1. Modified bovine milk proteins are also potent HIV-1 inhibitors and may have potential for anti-HIV-1 prophylaxis.

Anhydrides↗
PubMedDate not supplied

Structural requirements for and consequences of an antiviral porphyrin binding to the V3 loop of the human immunodeficiency virus (HIV-1) envelope glycoprotein gp120.

Several porphyrin derivatives were reported to have anti-HIV-1 activity. Among them, meso-teta(4-carboxyphenyl)porphine (MTCPP) and other carboxyphenyl derivatives were the most potent inhibitors (EC50 <0.7 mu M). MTCPP bound to the HIV-1 envelope glycoprotein gp120 and to full-length V3 loop peptides corresponding to several HIV-1 isolates but not to other peptides from gp120 + gp41. However, it remained possible that MTCPP bound to regions on gp120 which cannot be mimicked by peptides. Further characterization of the binding domain for MTCPP is important for understanding the antiviral activity of porphyrins and for the design of anti-HIV-1 drugs interfering with functions of the virus envelope. Results presented here show that: (i) deletion of the V3 loop from the gp120 sequence resulted in drastically diminished MTCPP binding, suggesting that the V3 loop is the dominant if not the only target site on gp120; (ii) this site was only partially mimicked by full-length V3 loop peptides; (iii) MTCPP binding to the gp120 V3 loop elicited allosteric effects resulting in decreased accessibility of the CD4 receptor binding site; (iv) the binding site for MTCPP lies within the central portion of the V3 loop (KSIHIGPGRAFY for the HIV-1 subtype B consensus sequence) and does not involve directly the GPG apex of the loop. These results may help in designing antiviral compounds with improved activity.

Allosteric Regulation↗
PubMedDate not supplied

Comparative molecular field analysis (CoMFA) of a series of symmetrical bis-benzamide cyclic urea derivatives as HIV-1 protease inhibitors.

A 3D-QSAR study using CoMFA methodology was conducted on a series of 29 symmetrical bis-benzamide cyclic urea derivatives having anti-HIV-1-protease activities. Active site minimization of the ligands was used to exclude conformations which are not sterically accessible within the active site. A significant cross validated correlation coefficient q2 (0.724) was obtained indicating the predictive potential of the model for untested compounds of this class. A significant non-cross-validated correlation coefficient (r2) of 0.971 with a low standard error estimate (S) of 0.119 was obtained indicating that the model reliably predicted the ant-protease activities of poorly to highly active compounds. The model was used to predict the anti-protease activities of eight test-set compounds, and the predicted values were in good agreement with the experimental values. The CoMFA coefficient contour plots identified several key features which explain the wide range of activities. The already reported 2D-QSAR along with the CoMFA model presented here may help in designing effective HIV-1 protease inhibitors.

Computer Simulation↗
PubMedDate not supplied

The importance of hydrophobicity in the mutagenicity of methanesulfonic acid esters with Salmonella typhimurium TA100.

The analysis of the mutagenic activity of a series of 15 methanesulfonate esters with Salmonella typhimurium TA100 shows that it can be correlated with the following equation: log TA100 = 1.10 log P + 0.73 log MMI -2.53, where MMI is the relative rate of reaction of the esters with N-methyl-2-mercaptoimidazole and P is the octanol/water partition coefficient. The results are compared with a number of other structure-activity studies on mutagenesis by a variety of types of chemicals.

Animals↗