Shiv Kumar

Antibacterial, cytotoxic activities and chemical composition of fruits of two Cameroonian Zanthoxylum species

ETHNOPHARMACOLOGICAL RELEVANCEnZanthoxylum leprieurii (Syn. Fagara leprieurii) is a plant extensively used by traditional healers in Cameroon for the treatment of stomach disorders, gonorrhea, intestinal parasites and sterility. The infusion from the fruit is taken in Cameroon for the treatment of sickle cell anemia, as well. Similarly, the roots of Zanthoxylum zanthoxyloides (Syn. Fagara zanthoxyloides) are also used for wound dressing, sickle cell anemia and as pain reliever, in addition to the uses mentioned for Zanthoxylum leprieurii.nnnAIM OF THE STUDYnTo scientifically validate their traditional use, the in vitro antimicrobial and anticancer assays were performed. In addition, chemical compositions of their fruit extracts and essential oils were also studied.nnnMATERIAL AND METHODSnThe chemical compositions of their essential oils and methanol extracts were studied. GC and GC-MS were used for analyzing the essential oils while various chromatographic methods were used to isolate the pure compounds from methanol extracts. MTT assay was used for the cytotoxic studies of methanol extracts, their fractions and some pure compounds. Antimicrobial activity of methanol extracts, some isolated compounds as well as essential oils was tested against a panel of human pathogenic bacteria by diffusion and dilution methods.nnnRESULTSnThe principal constituents of the essential oil of Zanthoxylum zanthoxyloides were identified as citronellol and geraniol whereas Zanthoxylum leprieurii was rich in E-β-ocimene. Furthermore, we report for the first time, the presence of 7,8-dimethoxycoumarin and sinapic acid in the methanol extract of Zanthoxylum leprieurii. In vitro bioassays reveal that the methanol extracts, essential oil and some of the isolated compounds from fruits of both the plants exhibit moderate anticancer and antimicrobial activities.nnnCONCLUSIONnAltogether, the present findings justify the traditional use of Zanthoxylum zanthoxyloides and Zanthoxylum leprieurii in the treatment of stomach disorders and cancer disease. The antimicrobial properties in the essential oil of Zanthoxylum zanthoxyloides are of additional significance.

Epoxide group relationship with cytotoxicity in withanolide derivatives from Withania somnifera.

Withania somnifera is one of the highly reputed medicinal plants of India. Its steroidal constituents exist in the form of two major substitution patterns, viz. withaferin A (1) and withanone (5). Withaferin A with oxidation at carbons 4, 5, and 6 is considered as an active type, especially as anticancer, whereas the withanones with oxidation at carbons 5, 6, and 7 rarely show any activity. We prepared a series of derivatives with modifications at carbons 5, 6, and 7 in ring B of these withanolides to study the role of the epoxide group towards the cytotoxic property of these bioactive steroids. We have converted withanolides into the respective thiiranes, amino alcohols and alcohols by selective reactions at the epoxide ring and were evaluated for in vitro anticancer activity against four cancer cell lines to study the structure activity relationships. The transformations of the epoxide group in withanolides of the withaferin A type showed moderate reduction in their cytotoxicity whereas the almost inactive withanones have shown some improvements in their alcohol derivatives.

Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species

BackgroundZanthoxylum zanthoxyloides and Z. leprieurii fruits are commonly used in traditional system of medicine for diarrhea, pain, wound healing, etc. in Cameroon, Africa. Z. leprieurii fruits have been chemically studied for its bioactive compounds whereas the investigation on Z. zanthoxyloides fruits is lacking.ResultsAfter a detailed chemical analysis of the fruits of Z. leprieurii and Z. zanthoxyloides, a series of new acridone alkaloids, namely, 3-hydroxy-1,5,6-trimethoxy-9-acridone (1), 1,6-dihydroxy-3-methoxy-9-acridone (2), 3,4,5,7-tetrahydroxy-1-methoxy-10-methyl-9-acridone (3), 4-methoxyzanthacridone (8), 4-hydroxyzanthacridone (9), 4-hydroxyzanthacridone oxide (2,4’) (10) have been isolated. The known acridones which have been characterized are, helebelicine A (4), 1-hydroxy-3-methoxy-10-methyl-9-acridone (5), 1,3-dihydroxy-4-methoxy-10-methyl-9-acridone (6) and tegerrardin A (7). The in vitro antibacterial and cytotoxic screening of these acridones reveal that compound 3 has a moderate antibacterial activity (MIC 125xa0μg/mL) against Micrococcus luteus and Pseudomonas aeruginosa while compound 1 shows a moderate cytotoxic effect (IC50 of 86xa0μM) against WRL-68 (liver cancer cell line). Furthermore, the molecular modeling of these acridones predicted the structural basis for their mode of action and binding affinity for aromatase, quinone reductase and WAAG, a glycosyltransferase involved in bacterial lipopolysaccharide synthesis. Computational approaches, quantitative SAR and modeling studies predicted that acridones 1, 2, 3, 4, 9 and 10 were the inhibitors of glycosyltransferase while 1, 8, 9 and 10, the inhibitors of aromatase.ConclusionsA total of 10 acridones have been isolated out of which 6 are new (1, 2, 3, 8, 9 and 10). Alkaloids 8, 9 and 10, having novel tetracyclic acridone structure with new carbon skeleton, have now been named as zanthacridone. The quantitative SAR and molecular modeling studies suggested that the compounds 1, 9 and 10 are inhibitors of both aromatase and glycosyltransferase.

Identification of 1-chloro-2-formyl indenes and tetralenes as novel antistaphylococcal agents exhibiting sortase A inhibition

Tetralene and indene compounds have shown inhibitory activity against human pathogen, Mycobacterium tuberculosis. Their potential use as antistaphylococcal agent against drug-resistant Staphylococcus aureus has not been explored so far. We determined in vitro antistaphylococcal activity and mechanism of action of these compounds as sortase A inhibitors through in silico analysis followed by biological assays. Tetralene and indene series were tested against S. aureus strains MTCC96, MRSA, and VA30. Three compounds showed significant reduction in MIC in both wild-type and drug-resistant S. aureus strains. In silico absorption, distribution, metabolism, excretion, and toxicity analysis of identified leads and cytotoxicity testing with colorimetric method using Vero and WRL-68 cell lines showed no significant cytotoxic effects. Molecular docking of these molecules with sortase A (PDB: 2KID) showed H-bond interaction with functional site residue Arg197 of sortase A. Sortase A inhibition assay was developed by expressing SrtA∆N from S. aureus strain MTCC96. Tetralene and indene compounds were found to have sortase A inhibitory potential. S. aureus strain MTCC96 treated with these compounds showed surface-sorting inhibition of fibronectin-binding protein and reduction in adherence to host extracellular matrix protein, fibronectin. 1-Chloro, 2-formyl, 6-methoxy, 1-tetralene (Tet-5), 1,5-dichloro, 2-formyl, 1-indene (Tet-20) and 1-chloro, 2-formyl, 5,6-methylenedioxy, and 1-indene (Tet-21) exhibited antistaphylococcal activity along with sortase A inhibition. The results also indicate the possible role of these leads in other reactions essential for cell viability.

Molecular Modeling Based Synthesis and Evaluation of In vitro Anticancer Activity of Indolyl Chalcones

A series of twenty one chalcone derivatives having indole moiety were synthesized and were evaluated against four human cancer cell lines. Indolyl chalcones 1a, 1b, 1d, 1f-1j, 2c, 2e, 2i showed good anticancer activity. Chalcones 1b and 1d were the most active and selective anticancer agents with IC50 values <1μg/ml and 1.51μg/ml, against WRL-68 cell line, respectively. Molecular mechanism was explored through in silico docking & ADMET studies.

ECONOMIC ANALYSIS OF CROSS-BRED COW MILK PRODUCTION VIS-À-VIS ECONOMIC TRAITS IN HARYANA

Districts of the Haryana State viz. Hisar and Karnal form important tract for the famous Haryana breed of cattle and Murrah breed of buffaloes. These districts were dominated with higher concentration in livestock population and infrastructural developments were selected purposely for this study. The multistage stratified random sampling technique was used for selection of the respondents. The study concluded that the age at first calving found to have considerable economic significance to the farmers because the cost of rearing heifer from birth to calving and consequently the milk yield are strongly influenced by this character. The milk yield and labour cost revealed inverse relationship with herd sizes. The net maintenance cost per milch cross-bred cow per day was highest in winter season and lowest in rainy season on all the herd size groups. The total feed and fodder cost constituted the most important item of the total cost accounting for about 63 to 68 per cent of the total cost across herd size group in different seasons. On an average, net profit of milk production of a cross-bred cow per day was the highest on small herd size group (Rs. 19.49) followed by medium (C. 18.62) and large size group (C. 18.01) in Karnal district. The net profit per cross-bred cow per day was higher in rainy season on all the herd size groups and the lowest in summer in case of small and large herd size groups and in winter in medium herd size group.