Muthuswami Kalyanasundaram

Larvicidal activity of Saraca indica, Nyctanthes arbor-tristis, and Clitoria ternatea extracts against three mosquito vector species

Screening of natural products for mosquito larvicidal activity against three major mosquito vectors Aedes aegypti, Culex quinquefasciatus, and Anopheles stephensi resulted in the identification of three potential plant extracts viz., Saraca indica/asoca, Nyctanthes arbor-tristis, and Clitoria ternatea for mosquito larval control. In the case of S. indica/asoca, the petroleum ether extract of the leaves and the chloroform extract of the bark were effective against the larvae of C. quinquefasciatus with respective LC50 values 228.9 and 291.5xa0ppm. The LC50 values of chloroform extract of N. arbor-tristis leaves were 303.2, 518.2, and 420.2xa0ppm against A. aegypti, A. stephensi, and C. quinquefasciatus, respectively. The methanol and chloroform extracts of flowers of N. arbor-tristis showed larvicidal activity against larvae of A. stephensi with the respective LC50 values of 244.4 and 747.7xa0ppm. Among the methanol extracts of C. ternatea leaves, roots, flowers, and seeds, the seed extract was effective against the larvae of all the three species with LC50 values 65.2, 154.5, and 54.4xa0ppm, respectively, for A. stephensi, A. aegypti, and C. quinquefasciatus. Among the three plant species studied for mosquito larvicidal activity, C. ternatea was showing the most promising mosquito larvicidal activity. The phytochemical analysis of the promising methanolic extract of the seed extract was positive for carbohydrates, saponins, terpenoids, tannins, and proteins. In conclusion, bioassay-guided fractionation of effective extracts may result in identification of a useful molecule for the control of mosquito vectors.

N,N-Diethyl Phenylacetamide (DEPA): A Safe and Effective Repellent for Personal Protection Against Hematophagous Arthropods

Abstract Repellents play an important role in protecting humans from the bites of insect pests. An effective and safe repellent will be useful in reducing human-vector contact and thereby help in the interruption of vector borne disease transmission. Because of the unavailability of m-toluic acid in India for the manufacture of N,N-diethyl m-toluamide (DEET), there is a need to develop an alternate effective and safe insect repellent. In total, 120 substituted amides were synthesized and tested for repellency at 1.0 mg/cm2 under laboratory conditions. Among these amides, N,N-diethyl phenylacetamide (DEPA), applied at 1.0 mg/cm2 in different oil bases, was found to exhibit promising repellency (6–8 h) in the laboratory when tested against Aedes aegypti (L.) The repellent DEPA was evaluated on army personnel in comparison with dimethylphthalate (DMP) and DEET against mosquitoes, black flies, and land leeches under field condition in the North-East Frontier area of India. Both DEPA and DEET displayed broad-spectrum repellency. DEPA was more effective than DMP against all test organisms. However, no significant difference was noticed between DEPA and DEET for repellency at 0.25 and 0.5 mg/cm2 against black flies and mosquitoes. DMP was the least effective among the three compounds in the field studies. The relative potency of DEPA in comparison with DEET and DMP for repellency against Phlebotomine sand flies also was determined. At 0.1 mg/cm2, both DEPA and DEET were found to be equally effective with a protection time from 4.37 ± 0.08 to 4.45 ± 0.15 h. Both compounds were significantly more effective than DMP. At 0.2 mg/cm2, DEPA and DEET provided protection times of 6.52 ± 0.08 and 7.15 ± 0.15 h, respectively. DEPA was formulated into a vanishing cream, a pharmacologically safe polymer-based liquid, and a liposphere lotion. The vanishing cream and the two-polymer liquid formulations enhanced protection times from 4.4 to 6.5 and 7.13 h, respectively, compared with an alcohol solution applied at 0.5 mg/cm2 on the forearm of human volunteers. Formulations of DEPA and DEET applied at 0.5 mg/cm2 on rabbits exposed to Ae. aegypti enhanced protection times compared with an alcohol solution and the liposphere lotion from 4.0 to 6.0 h and 4.0 to 5.0 h, respectively. Comparison of mean protection times of DEET and DEPA applied at a rate of 0.3 mg/cm2 to human volunteers exposed to Cx. quinquefasciatus under field conditions indicated that the lotion formulations of DEET and DEPA provided significantly (Duncan’s multiple-range test, P < 0.05) higher protection times than did alcohol solutions. Toxicological studies revealed that DEPA is safe.

Glutathione S-transferase (GST) inhibitors

The glutathione S-transferases (GSTs; EC 2.5.1.18) comprise a family of widely distributed Phase II detoxication enzymes that catalyse the conjugation of a broad variety of reactive electrophiles to the nucleophilic sulfur atom of the major intracellular thiol, the tripeptide glutathione. The diverse functions, including catalytic GSH conjugation, passive ligandin-type binding and modulation of signal transduction, may be selectively targeted by different inhibitors. GST inhibitors are emerging as promising therapeautic agents for managing the development of resistance amongst anticancer agents. In diagnostic medicine, as well as in antiparasitic drug development, GST inhibitors are important lead molecules. In this review, the important molecules known for their GST inhibition together with potential therapeutic uses are summarised.

A high performance liquid chromatographic method for the estimation of diethylcarbamazine content in medicated salt samples

A simple and reproducible method for the estimation of diethylcarbamazine citrate (DEC) by high performance liquid chromatography (HPLC) in DEC-medicated salt was developed. HPLC analysis was conducted with a mobile phase containing acetonitrile/phosphate buffer (20 mM KH(2)PO(4,) adjusted to pH 3.2 with 10% ortho-phosphoric acid) in the ratio of 1:9 and at a flow rate of 1.5 ml/min. A Phenomenex C8 column (15 cmx4.6 mm) of 5 microm particle size was used for the analysis. Analysis was done at UV 210 nm, 0.02 a.u.f. and 40 degrees C. The coefficient of variation was <10% in the range of 1-25 microg/ml and the minimum detectable level was 0.5 microg/ml. The quality of DEC-medicated salt prepared by two methods was analyzed by using the HPLC method. In spray drying method, 29 and 71% of the samples and in rotating drum method, 9 and 12% of samples were found to contain DEC at 0.15-0.25% and >0.25%, respectively. Thus, this quick and simple HPLC method for the estimation of DEC could play a vital role in checking the quality of the DEC medicated salt used for the control of filariasis.

Synthesis and screening of 1-methyl-4-substituted benzoyl piperazides against adult Setaria digitata for antifilarial activity

There is no safe and effective drug for killing the adult worms for the elimination/control of lymphatic filariasis and research is very much warranted towards the development of a macrofilaricidal drug. Therefore, the synthesis and evaluation of 1-N-methyl-substituted benzoyl/phenyl acetyl piperazides for macrofilaricidal activity were carried out. The title compounds, 1-N-methyl-substituted benzoyl/phenyl acetyl piperazides were synthesized and purified by slightly modifying the reported procedure and characterized by FT-IR, NMR and mass spectral data. The compounds were screened for macrofilaricidal activity against adult Setaria digitata, the bovine filarial worm for motility and MTT reduction assays using the reported procedures. All the compounds synthesized were characterized by spectral data. Out of 26 compounds synthesized and screened for macrofilaricidal activity, six compounds exhibited moderate antifilarial activity. The structure-activity relationships are discussed. In the case of benzoyl piperazides chloro-substitution in the para position enhanced the activity compared to its substitution in meta and ortho positions. In the case of phenyl acetyl piperazides when methyl group was in the meta position it was more active than when it was in para position. In dimethyl substituted compounds, substitutions at 3, 5-positions were more effective than 2, 3 and 3, 4 substitutions.