P. Suryanarayana Murthy

Antitubercular activity of trifluoperazine, a calmodulin antagonist

Trifluoperazine, a calmodulin antagonist, completely inhibited the growth of mycobacteria. The minimum inhibitory concentrations in shake cultures in a synthetic medium containing 0.2% Tween 80 were 5 and 8 micrograms/ml, respectively, for the human pathogenic strain Mycobacterium tuberculosis H37Rv and M. tuberculosis resistant to isoniazid. When added to a growing culture of M. tuberculosis H37Rv on the 10th day (mid exponential phase), trifluoperazine 50 micrograms/ml further arrested growth of this organism. It is suggested that trifluoperazine or similar calmodulin antagonists might be useful as antitubercular drugs.

Hypolipidemic effect of water extract ofFicus bengalensis in alloxan induced diabetes mellitus in rabbits

Hypolipidemic effect of the water extract of the bark ofFicus bengalensis was investigated in alloxan induced diabetes mellitus in rabbits. Treatment for one month (50 mg/kg body weight/day) brought down the level of total serum cholesterol (TC) in subdiabetic and diabetic rabbits (five in each group) from 82±11 mg% and 118±10.6 mg% to 42.7±3.1 mg% and 51.7±4.7 mg% respectively. Low density lipoprotein cholesterol and very low density lipoprotein cholesterol values came down from 34±10 mg% and 95±24 mg% to 16±3 mg% and 29±4 mg% in subdiabetic and diabetic rabbits. Triacylglycerol level before treatment was 121±21.6 mg% and 416±70 mg% in subdiabetic and diabetic rabbits. Treatment brought it down to 45±5 mg% and 81±27.5 mg%. Glycosylated hemoglobin was brought down from 2.1±0.3% to 1.5±0.1% in subdiabetic group and from 4.28±0.5% to 2±0.3% in diabetic group, indicating that treatment with water extract effectively controlled blood sugar.After treatment with water extract serum lipid values were nearly equal to those in healthy controls (normal) in subdiabetic rabbits, while in diabetic group, the values were only slightly above those of normal.

Hypocholesterolemic effect of water extract of the bark of banyan tree,Ficus bengalensis

The hypocholesterolemic effect of the water extract of the bark ofFicus bengalensis was investigated in 3 groups of rabbits, 5 in each group. Group 1 rabbits served as healthy controls and were fed with groundnut oil 1 ml/kg body wt. (bw) for five weeks. Groups 2 and 3 were made hypercholesterolemic by feeding orally cholesterol suspended in groundnut oil (1 ml/kg bw) at a dose of 100 mg/kg bw/day. Group 2 animals (untreated) continued to get the same amount of cholesterol for another four weeks. Group 3 animals received water extract of the bark (50 mg/kg bw/day) in addition to cholesterol as above. At the end of the 5th week, water extract not only prevented the elevation of serum cholesterol in the treated animals (Group 3) but also brought down its level to 160±14 mg% as compared to untreated animals (Group 2) 290±42 mg%. There was improvement in other parameters of lipid profile namely HDL & LDL+VLDL cholesterol and triacylglycerol.

Preliminary studies on the antitubercular activity and the mechanism of action of the water extract of garlic (Allium sativum) and its two partially purified proteins (Garlic defensins

Water extract of garlic (Allium sativum) inhibited the growth ofMycobacterium tuberculosis H37Rv andM. tuberculosis TRC-C1193 susceptible and resistant to isoniazid respectively. The minimum inhibitory concentration (MIC) was slightly above 80 but less than 160 μg/ml and slightly above 100 but less than 200 μg/ml for the susceptible and resistant strains respectively. Gel filtration in Sephadex G-100 columns showed that two protein fractions (43 & 38 kD) possessed antitubercular activity with much lower MICs of 20–40 μg/ml and 30–60 μg/ml for susceptible strain. Water extract, when added to actively growingM. tuberculosis in their mid log phase prevented their further growth. The water extract of garlic inhibited the incorporation of14C glycine into whole cells by 81% in 6 hrs. indicating that the primary mechanism of action is by inhibition of protein synthesis.

Purification and mechanism of action of antitubercular principle from garlic (Allium sativum) active against isoniazid susceptible and resistantMycobacterium tuberculosis H37Rv

Allicin was prepared from the ethanol extract of garlic without the use of heat. It inhibited the growth ofMycobacterium tuberculosis H37Rv andM. tuberculosis TRC-C 1193 resistant to isoniazid completely when grown as surface cultures as well as shake cultures. The minimum inhibitory concentration (MIC) was 70 μg/ml for both organisms. Further purification of allicin over silica gel-G columns gave a chloroform elutable fraction called CEF-allicin which inhibited the growth of both the susceptible and the isoniazid resistant strains ofM. tuberculosis. Its MIC is 25 μg/ml and is the lowest reported so far when compared with very high inhibitory concentration of 1 to 3mg/ml reported by other workers. It completely inhibited the synthesis of lipids and DNA from14C-acetate and3H-thymidine respectively and almost completely that of proteins and glycine derived carbohydrates from14C-glycine ofM. tuberculosis within 6 hr of exposure to CEF-allicin.

Partial purification of a hypoglycemic fraction from the unripe fruits ofMomordica charantia Linn (bitter gourd)

A new method was developed to purify partially an orally active hypoglycemic fraction from the unripe fruits ofMomordica charantia Linn. The residue after centrifugation of the fruit juice was extracted with ethanol and the concentrated ethanolic extract was further extracted with diethyl ether. In normal rabbits after oral administration, the ether extract at a dose of 0.75 g/kg body wt decreased the fasting blood glucose by 26% (P<0.01). It was compared with charantin, the isolation procedure of which led to loss of hypoglycemic activity many times. Our new method of isolation is simple and the hypoglycemic effect is retained more consistently after purification.

Inhibitory and bactericidal activity of the calmodulin antagonist, trifluoperazine, againstMycobacterium avium in vitro and within human monocyte-derived macrophages

The activity of a calmodulin antagonist, trifluoperazine (TFP), was testedin vitro againstMycobacterium avium (ATCC 25291). The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of this compound forM. avium were 20 and 30 μg/ml, respectively. TFP was also found to completely inhibit the growth of 10 isolates ofM. avium (5 patient isolates and 5 environmental isolates) at 30 μg/ml. At near neutral pH (6.8), the MIC of TFP was found to be 20 μg/ml. However, at pH 5.5 (intracellular pH of macrophages), there was a decrease in the inhibitory activity of the compound against this organism. Interestingly, 99.6% ofM. avium within human monocyte-derived macrophages were killed at a drug concentration of 30 μg/ml, which correlates well with the MBC of TFP againstM. avium in vitro. Although the MIC for TFP appears to be higher than that forMycobacterium tuberculosis H37Rv, our studies suggest that calmodulin antagonists might be useful as drugs against infection due toM. avium. It is suggested that administration of TFP in combination with other known drugs may enhance the overall bactericidal effect.

Effect of some antitubercular drugs on the calmodulin content ofMycobacterium tuberculosis

The effect of the antitubercular drugs isoniazid (10 μg/ml), ethambutol (10 μg/ml), rifampicin (0.5 μg/ml) and streptomycin (1 μg/ml) on the calmodulin like protein (CAMLP) content ofMycobacterium tuberculosis H37Rv andM. tuberculosis H37Ra was investigated. The drugs were added to actively growing cells at their mid log phase of growth (14 days) and after 12 more hours of incubation, CAMLP was estimated. In both the mycobacteria, all the four antitubercular drugs CAMLP.