Biomedical subjects

S P Gupta

Publications and source records attributed to S P Gupta.

At least 19 recordsLinked to original sources

PubMed2006

Transdermal atenolol releasing system: an approach towards its development.

A polymer matrix system for transdermal delivery of atenolol was developed for its prolonged and controlled release using different ratios of ethylcellulose and hydroxypropyl methylcellulose. These polymeric matrix films were characterized for thickness, tensile strength, moisture content and drug content. They were also studied for in vitro drug release and in vitro drug skin permeation. The drug release from the films was found to be Fickian diffusion type and exhibiting linear relationship between drug release (Q) vs. square root of time (t0.5). The in vitro skin permeation of drug from transdermal drug delivery system (TDDS) was evaluated using dermatomed pig skin. The product which shows in vitro drug skin permeation near to 64 mcg/h/ml was selected for in vivo studies. The in vivo studies revealed that Ma EC HPMC 46 is most effective among the other polymeric matrix TDDS. The AUC0-28 with Ma EC HPMC 46 was better than orally administered conventional doses at twelve hours interval (AUC0-28 1587 ng h/ml) as well as no trough and peaks in drug plasma level was recorded with TDDS. Hence, it could be concluded that the designed polymeric matrix TDDS of atenolol could be used successfully for effective and prolonged delivery of atenolol. However, it further demands exploration in clinic, an insight vision towards the development of TDDS for commercial use.

Administration, Cutaneous↗

PubMed2006

Quantitative structure-activity relationship studies on matrix metalloproteinase inhibitors: hydroxamic acid analogs.

A quantitative structure-activity relationship study has been conducted on two different series of acyclic hydroxamic acid analogs acting as matrix metalloproteinase (MMP) inhibitors. The results suggest that in a few cases, the hydrophobic property of the molecules is the major governing factor. However, in some cases, the polarizability of the molecules is shown to be dominant. The two enzymes, MMP-9 and MMP-13, are shown to behave in a similar fashion with any group of inhibitors.

Hydroxamic Acids↗

PubMed2005

A quantitative structure-activity relationship study on some series of anthranilic acid-based matrix metalloproteinase inhibitors.

A quantitative structure-activity relationship (QSAR) study has been made on four different series of anthranilic acid-based matrix metalloproteinase (MMP) inhibitors, in which two substituted aryl rings, one bearing the hydroxamic acid moiety that binds with the zinc atom of MMPs, are joined through a bridge group of sulfonamide. The QSAR results indicate that the sulfonamide group plays a very important role in the inhibition activity of the inhibitors and that the effectiveness of this sulfonamide group can be increased by the presence at the aryl rings or at the sulfonamide nitrogen itself of nitrogen-containing or some such substituents that can increase the electronic character of the sulfonamide group. The hydrophobic character of the molecules is not found to be of any advantage; rather in most of the cases it is shown to have detrimental effect, suggesting that MMPs provide little opportunity to the inhibitors to have a any hydrophobic interactions with them. On the other hand, polarizability of the molecules has been found to be conducive to activity in some cases. Thus the inhibition mechanism seems to predominantly involve the electronic interactions between the inhibitors and the enzymes.

Matrix Metalloproteinase Inhibitors↗

PubMed2005

A quantitative structure-activity relationship study on some aromatic/heterocyclic sulfonamides and their charged derivatives acting as carbonic anhydrase inhibitors.

A quantitative structure-activity relationship (QSAR) study is made on a series of aromatic/heterocyclic sulfonamides and their charged derivatives acting as carbonic anhydrase (CA) inhibitors. These compounds were studied by Scozzafava et al. (J. Med. Chem. 2000; 43: 292) for the selective inhibition of CAs--sulfonamides generally do not discriminate between different CA isozymes and hence exhibit many undesirable side effects when used as drugs against a particular disease. In this communication, an attempt has been made to investigate the physicochemical and structural properties that can make them selective for a given CA isozyme. Based on in vitro data reported by Scozzafava et al. against two cytosolic isozymes and one membrane-bound isozyme, the QSAR study has shown that uncharged compounds cannot be made selective for cytosolic or membrane-bound isozyme since in both the cases the compounds appear to follow the same mechanism of inhibition. However, for the charged compounds the polarizability of the molecule seems to greatly favor the inhibition of the membrane-bound enzyme, and hence they can be made selective for this enzyme by enhancing their polarizability, which is found to play no role in the inhibition of cytosolic enzymes.

Carbonic Anhydrase I↗

PubMed2005

Intraosseous neurilemmoma of L2 vertebra--a case report.

Intraosseous neurilemmoma (schwannoma) is a rare bone tumor with incidence less than 0.2% of all primary bone tumors. It is a benign neoplasm arising from the schwann cells of the nerve sheath. When they occur, they are usually found in the mandible. This paper reports an unusual occurrence of intraosseous neurilemmoma in L2 vertebral body. This patient presented with complaints of backache and progressively increasing weakness in both lower limbs. Roetengenograms showed an osteolytic lesion of L2 vertebra localized in the left half of the body and pedicle. Computed tomograph revealed a large soft tissue component of the tumor mass with thecal sac compression. A computed tomograph assisted needle biopsy revealed the tumor to be neurilemmoma. Subsequently, during decompression, it was possible to shell out tumor from surrounding tissues. Remaining tumor was curettedfrom bone and the cavity packed with autograft. The recovery was uneventful with incorporation of graft. The aim of this article is to highlight intraosseous neurilemmoma as a possible differential diagnosis in bony tumors. Intraosseous neurilemmoma of lumbar vertebrae is an extremely rare occurrence and till date only four cases are reported in English literature.

Adult↗

PubMed2004

Quantitative structure-activity relationship studies on some series of calcium channel blockers.

A quantitative structure-activity relationship (QSAR) study has been made on four different series of dihydropyrimidine analogs that mimic the most widely studied class of calcium channel blockers (CCBs)-the 1,4-dihydropyridine (DHP) class. The results show that almost all those characteristics that are essential for the activity of 1,4-DHPs are also essential for the activity of dihydropyrimidine analogs. The important characterstics indicated by the present study for dihydropyrimidine analogs are conformation of the molecule, the relative orientation of the aryl ring with respect to the pyrimidine ring, and some substituents capable of forming the hydrogen bonds with the receptor but less bulky in nature, and high molar refractivity of the molecule.

Animals↗

PubMed2004

A quantitative structure-activity relationship study on a series of Na+, K+-ATPase inhibitors.

A quantitative structure-activity relationship (QSAR) study has been made on a new series of digitalis-like Na+,K+-ATPase inhibitors in which the guanylhydrazone group has been replaced by an aminoalkyloxime group. The correlations obtained have shown that the oxime moiety, primary amine group, overall size, and polarizability of the new type of substituents are higly beneficial to the Na+,K+-ATPase inhibition potency of the compounds and that their effect can be quantitatively assessed. The study also showed that the inotropic activity of the compounds is very well correlated with their Na+,K+-ATPase inhibition potency.

Molecular Conformation↗

PubMed2003

A quantitative structure-activity relationship study on Clostridium histolyticum collagenase inhibitors: roles of electrotopological state indices.

A quantitative structure-activity relationship (QSAR) study has been made on eight different series of Clostridium histolyticum collegenase (ChC) inhibitors. These series are comprised of four different groups of sulfonylated amino acids and their corresponding hydroxamates. In each series, the inhibition potency of the compounds has been found to be significantly correlated with the electrotopological state (E-state) indices of nitrogen and sulfur atoms of the sulfonylated amino group in the molecules, showing the importance of the electronic characterstics of these atoms in controlling the inhibition potency of the compounds.

Alanine↗

PubMed2003

A quantitative structure-activity relationship study of hydroxamate matrix metalloproteinase inhibitors derived from functionalized 4-aminoprolines.

A quantitative structure-activity relationship (QSAR) study has been made on the inhibitions of some matrix metalloproteinases (MMPs) by functionalized 4-aminoproline based hydroxamates. Attempts have been made to correlate the inhibition potencies of these hydroxamates with Kier's first-order valence molecular connectivity index ((1)chi(v)) of substituents and electrotopological state (E-state) indices of some atoms. The correlations obtained for the inhibitions of all the enzymes studied, i.e. MMP-1, MMP-2, MMP-3, MMP-7, and MMP-13, were not so uniform, but suggested that in almost all the cases the substituents at the amide nitrogen may be conducive to the activity, though the whole amide group may be sterically unfavourable. Similarly, in most of the cases, the substituens at the phenyl moiety have been found to be beneficial to the inhibition potency and in many cases an electronic role of SO(2) group of the sulfonylphenyl moiety has been indicated.

Enzyme Inhibitors↗

PubMed2003

A quantitative structure-activity relationship study on some matrix metalloproteinase and collagenase inhibitors.

A quantitative structure-activity relationship (QSAR) study is made on some hydroxamic acid-based inhibitors of matrix metalloproteinases (MMPs) and a bacterial collagenase, namely Clostridium histolyticum collagenase (ChC), that also belongs to an MMP family, M-31, using Kier's valence molecular connectivity index (1)chi(v) of the substituents and electrotopological state (E-state) indices of some atoms. The results indicate that out of the four MMPs (MMP-1, MMP-2, MMP-8, and MMP-9) studied, MMP-2 and MMP-9 can be structurally quite similar, but widely differing from MMP-1 and MMP-8 and ChC. For MMP-2 and MMP-9, the inhibition activity of compounds is shown to depend on both (1)chi(v )and E-state indices, while for MMP-1 and MMP-8 it is shown to depend only on E-state indices and for ChC only on (1)chi(v). However, in all the cases, an aromatic group like C(6)F(5) or 3-CF(3)-C(6)H(4) attached to SO(2) moiety in the compounds is indicated to be equally beneficial, due to probably the involvement of fluorine atom(s) in charge-charge interactions with the Zn(2+) ion of the enzymes or in the formation of the hydrogen bonds with some sites of the receptors.

Benzene Derivatives↗

PubMed2003

A quantitative structure-activity relationship study on a novel class of calcium-entry blockers: 1-[(4-(aminoalkoxy)phenyl)sulphonyl]indolizines.

A quantitative structure-activity relationship (QSAR) study has been made on two different series of 1-[(4-(aminoalkoxy)phenyl)sulphonyl]indolizines acting as calcium entry blockers, using some physicochemical and structural parameters. Two different assays were reported for both the series: (IC(50))(A), referring to the molar concentration of the compound required to reduce [3H] nitrendipine binding by 50%, and (IC(50))(B), referring to that required to block Ca(2+) induced concentration of K(+) depolarised rat aorta by 50%. For series 1, where the 2-position substituents of indolizine ring were varied along with the aminoalkoxy moieties of the phenyl ring, the QSAR analysis shows that the 2-position substituents can equally affect both the activities through their hydrophobic and electronic properties and the aminoalkoxy moiety through some steric effects. For series 2, where the indolizine ring has been replaced by varying heterocyclic rings, along with the changes in aminoalkoxy moiety of the phenyl ring, the QSAR exhibits that these different heterocyclic rings affect both the activities through some steric roles, altering the conformations of the receptors from system A to system B. Among the different heterocyclic rings, the N-substituted indole ring is shown to be more conducive to both the activities than any other ring. However, a 5-membered ring is indicated to be less effective than a 9- or 10-membered ring for activity B. Additionally, the amino moieties having phenyl ring with methoxy groups at 3,4,and 5-positions are shown to favour both A and B activities.

Animals↗

PubMed2003

A comparative QSAR study on carbonic anhydrase and matrix metalloproteinase inhibition by sulfonylated amino acid hydroxamates.

A quantitative structure-activity relationship (QSAR) study is made on the inhibition of a few isozymes of carbonic anhydrase (CA) and some matrix metalloproteinases (MMPs), both zinc containing families of enzymes, by sulfonylated amino acid hydroxamates. For both enzymes, the inhibition potency of the hydroxamates is found to be well correlated with Kier's first-order valence molecular connectivity index 1chi(v) of the molecule and electrotopological state indices of some atoms. From the results, it is suggested that while hydroxamate-CA binding may involve mostly polar interactions, hydroxamate-MMP and hydroxamate-ChC (ChC: Clostridium histolyticum collagenase, another zinc enzyme related to MMPs) bindings may involve some hydrophobic interactions. Both MMPs and ChC also possess some electronic sites of exactly opposite nature to the corresponding sites in CAs. A group such as C6F5 present in the sulfonyl moiety is shown to be advantageous in both CA and MMP (also ChC) inhibitions, which is supposed to be due to the interaction of this group with Zn2+ ion present in the catalytic site of both families of enzymes.

Carbonic Anhydrase Inhibitors↗

PubMed2003

Design and development of integrase inhibitors as anti-HIV agents.

A review is presented on different categories of compounds that have been studied for the inhibition of the HIV-1 integrase to develop anti-HIV agents. These compounds are: oligonucleotides (double-stranded, triplex, and G-quartet), curcumin analogues, polyhydroxylated aromatic compounds, diketo acids, caffeoyl- and galloyl - based compounds, hydrazides and amides, tetracyclines, and depsides and depsidones. For all these compounds, the important structural features essential for the inhibition of the integrase are pointed out.

Amides↗

PubMed2001

Quantitative structure-activity relationships of antianginal drugs.

Quantitative structure-activity relationships (QSARs) of various classes of antianginal drugs, e.g. nitrates, beta-adrenergic blocking agents (beta-blockers), and calcium channel blockers (calcium antagonists), have been reviewed. This review gives an overall picture of the mode of action of each class of drugs and points out the specific physicochemical and structural properties that govern their activity. It is observed that in almost all kinds of antianginal drugs the lipophilic factor plays an important role and the next important factor seems to be the steric ones. The electronic factors are found to be occasionally important. In the case of beta-blockers, the most common factor that appeared to govern the activity remained the lipophilicity. In nitrates, too, the activity is observed to primarily depend upon the lipophilicity. In calcium channel blockers, however, the dominant effect is seen to be of steric factors. The steric roles may be essential in drug-receptor interactions, which seem to involve both hydrophobic, and to a lesser extent, electronic interactions.

Angina Pectoris↗

PubMed2001

A quantitative structure-activity relationship study on some HIV-1 protease inhibitors using molecular connectivity index.

A quantitative structure-activity relationship (QSAR) study has been made on two different series of tetrahydropyrimidinones acting as HIV-1 protease inhibitors. A structural parameter, the first order valence molecular connectivity index ((1)chi(v)), has been used to account for the variation in the activity. The protease inhibition activity as well as the antiviral potency of the compounds are found to be significantly correlated with (1)chi(v) of P(2)/P(2') substituents attached to the two nitrogens N1 and N3, suggesting that substituents containing less electronegative and more saturated atoms, meaning thereby the less polar or more hydrophobic substituents, will be more advantageous. Further, if P(2) and P(2') are dissimilar, the former is found to be more effective than the latter. This difference is attributed to a conformational change in the enzyme that may be more favorable to P(2) binding than to P(2') binding.

Anti-HIV Agents↗

PubMed2001

Quantitative structure-activity relationship of some HIV-1 protease inhibitors: a Fujita-Ban type analysis.

A Fujita-Ban type analysis has been made on a few series of HIV-1 (human immunodeficiency virus of type 1) protease inhibitors and the activity contributions of various substituents obtained. From these activity contributions, a compound is predicted that may have better activity than ritonavir, presently prescribed for the treatment of patients suffering from HIV-1. A few other compounds are also suggested.

Animals↗

PubMed2000

Quantitative structure-activity relationships of cardiotonic agents.

Quantitative structure-activity relationships (QSARs) of different cardiotonic agents are presented. A critical analysis of all QSARs provides a very vivid picture of the mechanisms of varying cardiotonic agents. The cardiotonics can be broadly put into 2 categories: cardiac glycosides and nonglycoside cardiotonics, which include phosphodiesterase of type III (PDE III) inhibitors, sympathomimetic (adrenergic) stimulants, A1-selective adenosine antagonists, Ca2+ channel activators and vasopressin antagonists. For cardiac glycosides, QSARs reveal that the position of carbonyl oxygen in their lactone moiety and shifting of the lactone ring from its original position or its replacement by another group would be crucial for their activity. The carbonyl group or its isostere like CN is indicated to be the sole binding entity and the hydrogen bonding through this group is considered to be the most likely binding force. For nonglycoside cardiotonics that include PDE III inhibitors and A1-selective antagonists, a five-point model has been established for their activity, the salient features of which are: (1) the presence of a strong dipole, (2) an adjacent acidic proton, (3) a methyl-sized lipophilic space, (4) a relatively flat overall topography and (5) a basic or hydrogen-bond acceptor site opposite to the dipole. For Ca2+ channel activators, the importance of steric, electrostatic, lipophilic and hydrogen-bonding properties of molecules is indicated, while for vasopressin antagonists the lipophilic and electronic properties are suggested to be the most important.

Animals↗

PubMed1999

Quantitative structure-activity relationships of antihypertensive agents.

Quantitative structure-activity relationships of various classes of antihypertensive agents, e.g., sympatholytic agents, diuretics, direct or peripheral vasodilators, potassium channel activators, angiotensin-converting enzyme inhibitors, renin inhibitors and miscellaneous agents (platelet aggregation inhibitors) are reviewed. This review gives an overall picture of the mode of action of each class of drugs and points out their specific physicochemical and structural properties governing their action. For example, in the case of centrally acting drugs (sympatholytic agents) it has surfaced that the prime factors governing their activity are lipophilic and steric properties of the molecules, and at the receptor level a charge-transfer complex is formed between the molecule and the receptor. It is, however, observed that for peripherally acting sympatholytic agents the prime role is played by only lipophilicity. In the case of diuretics, the electronic characters of molecules are found to be more dominant than their lipophilic property, but for direct vasodilators and ACE inhibitors both electronic and lipophilic properties seem to be equally important. In renin or platelet aggregation inhibitors, the structural properties appear to be more important. However, the fundamental property that is overwhelmingly involved in the majority of antihypertensive agents appears to be the lipophilicity, suggesting that in most of the cases the hydrophobic interaction would play the major role in drug action.

Animals↗