Biomedical subjects

Rajeshwar P Verma

Publications and source records attributed to Rajeshwar P Verma.

At least 19 recordsLinked to original sources

PubMed2006

Understanding human rhinovirus infections in terms of QSAR.

The human rhinoviruses (HRVs) are the single most important cause of common colds. The widespread nature of this affliction, the economic consequences, and the well-known impracticality of vaccine development due to the large number of HRV serotypes (>100) have justified the search for chemotherapeutic agents. The interest in the application of quantitative structure-activity relationships has steadily increased in recent decades and we hope it may be useful in the search for anti-HRV agents. In the present paper, we have discussed the inhibition of various six compound series against HRV-1A, -1B, -2, -9, -14, -21, -22, -25, -64, and -89 by the formulation of a total number of 14 QSAR. Hydrophobicity is found to be one of the most important determinants of activity. Parabolic correlation with the hydrophobic parameter (Eq. ) is an encouraging example, where the optimal hydrophobicity is well defined. We believe that this may be the predictive model to narrow the synthetic challenges in order to yield very specific HRV-2 inhibitors. On the basis of this model, we have predicted eleven compounds (I-1 to I-11) that may be the next synthetic target. The proposed molecules (I-1 to I-11) also fulfill the conditions of Lipinski's "rule of five".

Antiviral Agents↗

PubMed2006

Chemical Toxicity on HeLa Cells.

HeLa cells were named for Henrietta Lacks, who died in 1952 from an infection of a special type of cancer. Margaret Gey, her physician, started working with these cancer cells that are still used for medical research. In the present review, an attempt has been made to collect the data for the effects of different chemicals on HeLa cells and to discuss them by the formulation of a total number of 22 QSAR.

HeLa Cells↗

PubMed2006

A classical QSAR study on some platelet aggregation inhibitors.

Cardiovascular diseases are still the main cause of morbidity and mortality in the world. Anti-platelet drugs have found clinical application in the secondary prevention of vascular events including acute myocardial infarction, stroke and cardiovascular death. In the present review, we have developed sixteen quantitative structure-activity relationships (QSAR) for different sets of compounds that are X-phenols (I), X-catechols (II), caffeic acid amides (III), X-alcohols (IV), 1,4-naphthoquinones (V), tetrahydronaphthalenes (VI), phenoxyacetaldehyde guanylhydrazones (VII), pyrrolobenzylisoquinolines (VIII) and phosphonic acids (IX) with respect to their anti-platelet activities. QSAR results have shown that the anti-platelet activities of these compounds are largely dependent not only on their hydrophobicity, but also on the influence of their molar refractivity.

Humans↗

PubMed2006

Understanding apoptosis in terms of QSAR.

Apoptosis is a cellular mechanism by which unwanted, defective, or damaged cells are rapidly and selectively eliminated to maintain healthy tissue homeostasis in multi-cellular organisms. In this review, we have developed nineteen quantitative structure-activity relationships (QSAR) for different series of compounds with respect to their apoptotic activities against five different cancer cell lines that are T47D, ZR75-1, DLD-1, H1299, and HL60 in order to understand chemical-biological interactions.

Apoptosis↗

PubMed2006

Anti-cancer activities of 1,4-naphthoquinones: a QSAR study.

Quinone moieties are present in many drugs such as anthracyclines, daunorubicin, doxorubicin, mitomycin, mitoxantrones and saintopin, which are used clinically in the therapy of solid cancers. The cytotoxic effects of these quinones are mainly due to the following two factors: (i) inhibition of DNA topoisomerase-II and, (ii) formation of semiquinone radical that can transfer an electron to oxygen to produce super oxide, which is catalyzed by flavoenzymes such as NADPH-cytochrome-P-450 reductase. Both semiquinone and super oxide of quinones can generate the hydroxyl radical, which is the cause of DNA strand breaks. 1,4-naphthoquinone contains two quinone groups that have the ability to accept one or two electrons to form the corresponding radical anion or di-anion species. It is probably dependent on the quinone redox cycling that yields "reactive oxygen species" (ROS) as well as arylation reactions, which is common to quinones for biological relevance. In the present review, an attempt has been made to collect the cytotoxicity data on different series of 1,4-naphthoquinones against four different cancer cell lines that are L1210, A549, SNU-1, and K562, which were acquired by using identical method, and has been discussed in terms of QSAR (quantitative structure-activity relationships) to understand the chemical-biological interactions. QSAR results have shown that the cytotoxic activities of 1,4-naphthoquinones depend largely on their hydrophobicity.

Animals↗

PubMed2005

Cellular apoptosis and cytotoxicity of phenolic compounds: a quantitative structure-activity relationship study.

In this comprehensive study on the caspase-mediated apoptosis-inducing effect of 51 substituted phenols in a murine leukemia cell line (L1210), we determined the concentrations needed to induce caspase activity by 50% (I50) and utilized these data to develop the following quantitative structure-activity relationship (QSAR) model: log 1/I50 = 1.06 B5(2) + 0.33 B5(3) - 0.18pi(2,4) - 0.92. B5(3) and B5(2) represent steric terms, while pi(2,4) represents the hydrophobic character of the substituents on the ring. The strong dependence of caspase-mediated apoptosis on mostly steric parameters suggests that the process is a receptor-mediated interaction with caspases or mitochondrial proteins being the likely targets. Conversely, cytotoxicity studies of 65 electron-releasing phenols in the L1210 cell line led to the development of the following equation: log 1/ID50 = -1.39sigma+ - 0.28 B5(2,6) + 0.16 log P - 0.58I(2) - 1.04I(1) + 3.90. The low coefficient with log P may pertain to cellular transport that may be enhanced by a modest increase in overall hydrophobicity, while the presence of sigma+ is consistent with the suggestion that radical stabilization is of prime importance in the case of electron-releasing substituents. On the other hand, the QSAR for the interactions of 27 electron-attracting phenols in L1210 cells, log 1/ID50 = 0.56 log P - 0.30 B5(2) + 2.79, suggests that hydrophobicity, as represented by log P is of critical importance. Similar cytotoxicity patterns are observed in other mammalian cell lines such as HL-60, MCF-7, CCRF-CEM, and CEM/VLB. The significant differences between the cytotoxicity and apoptosis QSAR for electron-releasing phenols suggest that cytotoxicity involves minimal apoptosis in most of these substituted monophenols.

Animals↗

PubMed2005

A QSAR study on influenza neuraminidase inhibitors.

Influenza is a major respiratory infection associated with significant morbidity in the general population and mortality in elderly and high-risk patients. It is an RNA virus that contains two major surface glycoproteins, neuraminidase and hemagglutinin. These proteins are essential for infection. Neuraminidase has been found to be a potential target to control influenza virus. In this paper, we have developed 17 quantitative structure-activity relationships (QSAR) for different sets of compounds to understand chemical-biological interactions governing their activities toward influenza neuraminidase.

Amides↗

PubMed2005

A QSAR review on melanoma toxicity.

Melanoma is one of the most aggressive forms of skin cancer and is currently attracting our attention particularly in the area of quantitative structure-activity relationships (QSAR). In the present review, an attempt has been made to collect the data for different sets of compounds and to discuss their toxicities toward melanoma cells by the formulation of a total number of 36 QSAR.

Animals↗

PubMed2005

An approach toward the problem of outliers in QSAR.

Compounds that have unexpected biological activity and are unable to fit in a QSAR model are known as outliers. These are valuable in defining the limitations under which compounds act by a common molecular mechanism modeled by one or more descriptors, and also in defining the experimental limitations of the biological test data. Thus, the outliers should be submitted to particular attention to see if the reason for their peculiarity can be determined. Separating these outliers from the main data set and formulating another QSAR can resolve the problem. Our result shows that these outliers may be acting by a different mechanism or interacting with the receptor in different modes.

Animals↗

PubMed2005

The role of hydrophobic properties of chemicals in promoting allosteric reactions.

An allosteric reaction has been found in a variety of instances where an inverted parabolic relationship between biological activity and hydrophobicity is apparent, that is the activity first decreases as hydrophobicity increases and after a certain point, activity begins to increase. This could be attributed to the ligands causing a change in the receptor structure. In this report, the role of hydrophobic properties of chemicals in promoting allosteric reactions have been discussed in term of hydrophobicity (logP) by the formulation of a total number of 50 QSAR equations. The QSAR model of this type may be represented by Eq. I.

Allosteric Regulation↗

PubMed2005

The role of QSAR in dopamine interactions.

Dopamine receptor blockers have been used for the treatment of schizophrenia for many years. We have developed 22 quantitative structure activity relationships (QSAR) for different sets of compounds to understand chemical-biological interactions governing their activities toward dopamine receptors.

Dopamine Agents↗

PubMed2005

A comparison between two polarizability parameters in chemical--biological interactions.

The polarizability of a molecule, an important physical property, is currently attracting our attention particularly in the area of QSAR (quantitative structure-activity relationships) for chemical-biological interactions. Our primary focus in the present study has been upon the computational aspects by using NVE (sum of the valence electrons) as a means for estimating polarizability, we have been surprised at its utility. In this report we demonstrate how NVE can be related to the calculated polarizability from a variety of efforts to better understand the subject. A comparison between the use of two polarizability parameters, that is, NVE and CMR (calculated molar refractivity) in the formulation of QSAR for chemical-biological interactions has been also discussed.

Computer Simulation↗

PubMed2005

Chemical-biological interactions in human.

Chemical-biological interactions in human are currently attracting our attention particularly in the area of QSAR (quantitative structure-activity relationships). In the present review, an attempt has been made to collect the data for the effect of chemicals in human and discussed by the formulation of a total number of 37 QSAR.

Biology↗

PubMed2005

Understanding topoisomerase I and II in terms of QSAR.

A variety of antitumor agents currently used in chemotherapy or evaluated in clinical trials are known to inhibit DNA topoisomerase I or II. We have developed sixteen quantitative structure-activity relationships (QSAR) for different sets of compounds that are camptothecin analogs, 1,4-naphthoquinones, unsaturated acids, benzimidazoles, quinolones, and miscellaneous fused heterocycles to understand chemical-biological interactions governing their inhibitory activities toward topoisomerase I and II.

DNA Topoisomerases, Type I↗

PubMed2005

On the role of polarizability in QSAR.

The polarizability of a molecule, an important physical property, is currently attracting our attention particularly in the area of QSAR for chemical-biological interactions. In this report, the polarizability effects on ligand-substrate interactions has been discussed in terms of NVE (number of valence electrons) using additive values for valence electrons and the formulation of a total number of 51 QSAR. The QSAR model can be illustrated by Eq. I. log 1/C = a(NVE) +/- constant

Ligands↗

PubMed2004

Elucidation of structure-activity relationships for 2- or 6-substituted-5,8-dimethoxy-1,4-naphthoquinones.

1,4-Naphthoquinones have already been recognized to possess a wide range of biological activities. We have developed quantitative structure activity relationships (QSAR) for different series of 2- or 6-substituted-5,8-dimethoxy-1,4-naphthoquinones to understand the chemical-biological interaction governing antiproliferative/cytotoxic activities against L1210 cells. QSAR results have shown that these activities of 2- or 6-substituted-5,8-dimethoxy-1,4-naphthoquinones depend largely on their hydrophobicity.

Animals↗

PubMed2004

An Approach towards the quantitative structure-activity relationships of caffeic acid and its derivatives.

Caffeic acid and its derivatives are already known to possess a wide range of biological activities. We have developed quantitative structure-activity relationships (QSARs) for different series of caffeic acid derivatives (including caffeic acid) in order to understand the chemical-biological interactions governing antitumor activity against six different tumor cell lines, nitric oxide production, anti-HIV and enzymatic activities, and binding affinity to the lck domain. QSAR results have shown that the different activities of caffeic acid and its derivatives are largely dependent on their hydrophobicity or molar refractivity, with a bilinear correlation being the most important.

Algorithms↗

PubMed2003

Synthesis, cytotoxicity, and QSAR analysis of X-thiophenols in rapidly dividing cells.

In this study, the cytotoxicities of a series of X-thiophenols vs rapidly growing mouse leukemia cells in vitro are determined. The resulting ID(50) values are then used to formulate a quantitative structure-activity relationship, which is well-correlated by the Brown variation of the Hammett electronic parameter, sigma-plus (sigma(+) ), such that Log 1/ID(50) = -0.93 (+/-0.18) sigma(+) + 0.86 (+/-0.24) I(H) + 3.99 (+/-0.13). I(H) represents an indicator variable that calls attention to the unusual activity of halogens and pseudohalogens. In lieu of sigma(+), homolytic bond dissociation energies (BDE) are also used successfully to correlate the cellular cytotoxicities of thiophenols. The nature of substituent effects on cellular toxicity is examined, and they reveal that electron-releasing substituted thiophenols such as 4-amino thiophenol and the 4-alkoxy thiophenols are highly cytotoxic and effective at inhibiting cellular proliferation at physiological pH. On the other hand, electron-attracting substituted thiophenols such as the 4-cyano and 4-halogen analogues show a reduced ability to inhibit the cell growth of this cell line. Thus, there is a clear parallel between enhanced biological activity and electron releasing ability as measured by sigma(+) constants or BDE values. The susceptibility of the cellular interaction to electronic effects as delineated by the coefficient with the sigma(+) term (also called the Hammett rho value) is high (-0.96), suggesting that substantial energetic assistance is provided by the substituents and that a weak initiating radical reactant such as superoxide radical may be involved. Previous cytotoxicity studies of a large diverse data set of X-phenols in this cell line and embryo cells have also revealed a more pronounced dependence on sigma(+) and deltaBDE. A comparison of reaction constants obtained from thiophenoxy radical formation reactions and phenoxy radical formation reactions in organic media suggests radical-mediated involvement in cell cytotoxicity. Such cells could be more vulnerable to the effects of reactive thiyl species on their metabolism and subsequent proliferation.

Animals↗