QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP (QSAR) STUDIES ON SOME CANCER CHEMOTHERAPEUTIC AGENTS
Fourteen Glutamine Analogs of the type 5-N-substituted- 2-(3',4'-disubstituted benzenesulphonyl) glutamine (1) weresynthesized as a part of composite programme of Rational DrugDosing [1]. These compounds were prepared by chlorosulphonationof chlorobenzene (2) and 1, 2-dichlorobenzene (3)respectively to get substituted benzenesulphonyl chlorides (4)which on condensation with glutamic acid (5) gave 2-(3' , 4'-disubstituted benzenesulphonyl)-5-oxopyrrolidine-2-carboxilicacids (7) which were aminated with respective amines (8). Allthe compounds were characterized both chemically andinstrumentally. When evaluated against Ehrlich AscitesCarcinoma (EAC) cell line in Swiss Albino mice (18-20 g) of thesame age and sex, using 2X106 cell inoculated i.p. and challengecompounds were administered i.p. for 7 days after 24 hrincubation of tumor cells, for tumor weight and cell countparameters, some of the compounds showed excellent anticanceractivities compared with the standard drug mitomycin C.Quantitative Structure Activity Relationship (QSAR) studies wereperformed with the help of Free Wilson's De Novo model.Excellent Correlation (correlation coefficient: r=0.90) wereobtained. The work showed the excellent yields of the synthesizedcompounds and some of synthesized compounds shownexcellent anticancer activities. Chemical structures wereexcellently correlated with the biological activities. The QSARstudy approved the additivity model of Free Wilson analysis andshowed that, individual substituent group contribution can beuseful to predict biological activity of compounds which are notsynthesized yet to get a fruitful 'lead' of anticancer drugs.
PHENOLIC AND POLYPHENOLIC COMPOUNDS INSOME MEDICINAL PLANTS AS NATURAL ANTIMUTAGENS:
Since the beginning of human civilization, man has been usingplants for medicinal purposes. The medicinal value of plants isdue to the presence of certain secondary metabolites, such asalkaloids, glycosides, terpenoids, flavins, resins, gums and tannins of the various secondary metabolites, phenoliccompounds are ubiquitous in edible vegetables, fruits and nuts.Naturally occurring phenolic compounds, including tannins, havebeen extensively studied for their inhibitory effect on the toxic,mutagenic and carcinogenic action of a wide array of chemicalmutagens and carcinogens with an aim to use them eventuallyas therapeutic/chemopreventive agents. Many of the plantscontaining polyphenols and tannins are being prescribed byAyurvedas and Hakeems as medicines. Many of these, such astea, containing phenolic compounds are being used daily. Thepresent investigation is aimed at fractionation of crude extractsfrom the bark of Terminalia arjuna, and Terminalia chebula inorder to isolate and purify the antimutagenic factor(s) present.Various spectroscopic techniques, viz. 1H-NMR, normal 13CNMR,distortionless enhancement by polarization transfer (DEPT-90 and DEPT-135), UV and IR, were used to analyze the chemicalcharacteristics of various isolated fractions. These fractions werefound to be triterpine diglycoside, triterpenes, ellagic acid,anthocyanins, etc, The antimutagenic assay was performed tocheck the modulatory effect of extracts/fractions using AmesSalmonella his+ reversion assay against directacting mutagen(NPD) and S9-dependent mutagen (2AF) and acid black dye. Itwas observed that some of the fractions showed 100% inhibitionof histidine mutants induced by direct-acting as well as s9-dependent mutagens and harboured constituents with promisingantimutagenic/anticarcinogenic potential which need to be furthertapped in the battery of test assays. The work is in progress todecipher their mechanism of action.
About the Author:
drizharnium@gmail.com, Bangalore India
Hi Friends, I am Izhar, love all of you, and I'd like to write about my interest, and here i am sharing about my opinion, prevention regarding to many diseases, maintaining views for Health, Beauty & Younger looking Secrets at article base.