Chandana Sengupta

QSAR modeling for lipid peroxidation inhibition potential of flavonoids using topological and structural parameters

In the present study, Quantitative Structure-Activity Relationship (QSAR) modeling has been carried out for lipid peroxidation (LPO)-inhibition potential of a set of 27 flavonoids, using structural and topological parameters. For the development of models, three methods were used: (1) stepwise regression, (2) factor analysis followed by multiple linear regressions (FA-MLR) and (3) partial least squares (PLS) analysis. The best equation was obtained from stepwise regression analysis (Q2 = 0.626) considering the leave-oneout prediction statistics.

QSAR modeling of antiradical and antioxidant activities of flavonoids using electrotopological state (E-State) atom parameters

In the present paper QSAR modeling using electrotopological state atom (E-state) parameters has been attempted to determine the antiradical and the antioxidant activities of flavonoids in two model systems reported by Burda et al. (2001). The antiradical property of a methanolic solution of 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and the antioxidant activity of flavonoids in a β-carotenelinoleic acid were the two model systems studied. Different statistical tools used in this communication are stepwise regression analysis, multiple linear regressions with factor analysis as the preprocessing step for variable selection (FA-MLR) and partial least squares analysis (PLS). In both the activities the best equation is obtained from stepwise regression analysis, considering, both equation statistics and predictive ability (antiradical activity: R2 = 0.927, Q2 = 0.871 and antioxidant activity: R2 = 0.901, Q2 = 0.841).

QSAR With Electrotopological State Atom Index: Human Factor Xa Inhibitor N 2 -Aroylanthranilamides

Recently, N2-aroylanthranilamides have been reported as novel series of possible anticoagulant drug candidates and the two aryl rings (A and B) have been suggested to interact with S1 and S4 regions, respectively, of human factor Xa (hfXa). In the present effort, quantitative structure-activity relationship (QSAR) of the hfXa binding affinity of 32 N2-aroylanthranilamides have been attempted, in continuation of our previous report on the QSAR analysis of the data set using linear free energy related (LFER) model, with electrotopological state atom (ETSA) index (Kier and Hall, 1991, Adv. Drug Design., 22, 1-38), to explore the atoms/regions of the compounds that modulate the activity comparatively to the greater extent. The univariate and bivariate relations involving the ETSA values of different common atoms of the compounds show importance of the atom nos. 12, 3 and 17 (arbitrary numbering): B ring carbon bearing meta R2 substituents, C ring carbon bearing R4 substituent, and carbonyl oxygen of A ring amide linkage. The importance of atom 12 is suggested to be due to detrimental effects of meta R2 substituents (B ring) on the hfXa binding affinity, which may be owing to interference in the attainment of the proper orientation of the phenyl ring in the S4 site. Atom 3 signifies the impact of R4 substituents (central C ring) on the binding affinity. Again, atom 17 (carbonyl oxygen of A ring amide linkage) has been suggested to form hydrogen bonding with the NH group of the other amide linkage, producing a pseudo ring and thus stabilizing the structure. The relations were improved further using indicator and physicochemical variables and the present results are in good agreement with the previous findings of the Hansch analysis.

Evaluation of protective effects of water extract of Spirulina platensis (blue green algae) on cisplatin-induced lipid peroxidation

Attempt has been made to evaluate free radical scavenging activity of water extract of Spirulina platensis on cisplatin-induced lipid peroxidation using some common laboratory markers. In this present study goat liver has been used as lipid source. This in vitro evaluation was done by measuring the malondialdehyde, 4-hydroxy-2-nonenal, reduced glutathione and nitric oxide content of tissue homogenates. The results suggest that cisplatin could induce lipid peroxidation to a significant extent and it was also found that water extract of the algae has the ability to suppress the cisplatin-induced toxicity.

Cysteine, a chelating moiety for synthesis of technetium-99m radiopharmaceuticals—Part IV. Benzyl cysteine and derivatives

To explore the possibility of utilizing cysteine derivatives for technetium-99m radiopharmaceutical preparation with clinical potential, we synthesized two benzyl substituted cysteine compounds, namely, S-benzyl cysteine 1 and cysteine benzyl ester 3. It was expected, from our previous studies on benzoyl cysteines, that the above two ligands after chelation with 99mTc would be excreted by the hepatobiliary pathway. Although for 99mTc-3 the above expectation was realized, 99mTc-1 behaved in a most unexpected way by affixing itself with kidney and selecting the renal tubular secretory pathway for its excretion. It is anticipated that the affinity of 99mTc-1 for kidney is due to its interaction with the kidney sulphhydryl group and it also formed an adduct with other sulphydryl containing compounds like thiophenol. In terms of the kidney-to-background ratio, 99mTc-1 showed some superiority over other kidney structure agents, like 99mTc-dimercaptosuccinic acid and 99mTc-glucoheptanoic acid and, therefore, the chelate (99mTc-1) may have the potential to replace the above two radiopharmaceuticals in clinical use.

QSAR of human factor Xa inhibitor N2-aroylanthranilamides using principal component factor analysis.

Quantitative structure-activity relationship (QSAR) study of human factor Xa inhibitor N2-aroylanthranilamides, recently reported by Yee et al. (J. Med. Chem., 43, 873-882), has been performed using principal component factor analysis as the preprocessing step. The study reveals that presence of electron-donating R2 substituent at the para position (with respect to the amide linkage) is conducive to the binding affinity, whereas a meta R2 substituent decreases the affinity. Again, electron-donating R1 substituents with less bulk and optimum hydrophilic-lipophilic balance (particularly, methyl and methoxy groups) favor the activity. The study further suggests that electron-withdrawing R3 substituents are detrimental for the activity, whereas bulkier R4 substituents (particularly NHSO2Me group) increase the activity.

QSAR of Antimalarial Cyclic Peroxy Ketals II: Exploration of Pharmacophoric Site Using AM1 Calculations

A series of antimalarial cyclic peroxy ketals (n=20) have been subjected to energy minimization using AM1 method, and Wang–Ford charges of the non-hydrogen common atoms (Figure 1), obtained from molecular electrostatic potential surface of the energy minimized geometries, have been used to model the antimalarial activity against P. falciparum. It is found that the difference in charges between the peroxy oxygens contribute positively to the activity, and this is in good agreement with the mode of antimalarial action of the peroxy compounds involving breakage of the peroxy bridge by the haem-iron within the parasite. It is hypothesized that difference in charges between two peroxy oxygens may facilitate the bond breakage. It is further found that the activity increases with increase in negative charge of the methoxy carbon of the common fragment of the molecule. This is related with possible secondary electronic interaction with the positively charged side chains of the histidine rich protein of P. falciparum. Attempt was made to incorporate steric and indicator parameters which emerged as important contributors from previous Hansch analysis. The present results support the previous observations that bulky phenyl ring substituents and a seven-member carbocylic ring attached to the peroxy bridge-containing ring are conducive to the activity.

Cisplatin-induced lipid peroxidation and its inhibition with Ascorbic acid

The aim of the study was to investigate the antiperoxidative potential of ascorbic acid on cisplatin-induced lipid peroxidation, using some common laboratory markers. Goat liver was used as the lipid source. This in vitro evaluation was done by measuring the malondialdehyde, 4-hydroxy-2-nonenal, reduced glutathione, and nitric oxide content of tissue homogenates. The results suggest that cisplatin could induce lipid peroxidation to a significant extent, and it was also found that ascorbic acid has the ability to suppress the drug-induced toxicity.

Exploring QSAR of hydroxyphenylureas as antioxidants using physicochemical and electrotopological state atom parameters

In the present study, free radical scavenging activity of 36 substituted hydroxyphenylurea derivatives was subjected to classical quantitative structure–activity relationship (QSAR) analyses using physicochemical (hydrophobicity and molar refractivity) and electrotopological state atom parameters. For the development of the QSAR models, statistical techniques such as stepwise multiple linear regression and genetic function approximation (GFA) were used. The developed models indicate an important contribution of the phenolic hydroxyl group of hydroxyphenylureas, apart from that of the urea moiety and piperazine nucleus of the side chain, to the free radical scavenging activity. The presence of substituents at the phenyl ring influences the electron density distribution over the phenolic ring system and modulates the activity. Hydrophobicity is found to contribute positively to the free radical scavenging activity. Based on internal validation (Q 2), external validation ( ) and overall validation criteria ( ), a GFA model with spline options was found to be the best model (Q 2 = 0.957, = 0.966, = 0.914).

The triglyceride composition ofMoringa concanensis seed fat

Moringa concanensis seed fat and its randomized product have been subjected to pancreatic hydrolysis. Glyceride compositions have been calculated from the original fatty acid composition and those of the monoglycerides produced by hydrolysis. The per cent GS3 content of the interesterified product has also been determined by the combined techniques of thin layer chromatography on silver nitrate impregnated silica gel and colorimetry.