Synthesis, Electrochemical Studies, Molecular Docking, and Biological Evaluation as an Antimicrobial Agent of 5-Amino-6-cyano-3-hydroxybenzo[c]coumarin Using Ni-Cu-Al-CO3 Hydrotalcite as a Catalyst.

New insights via a multicomponent cyclocondensation reaction of 2-hydroxy benzaldehyde acetoacetic ester and malononitrile were attained under efficient conditions. A detailed mechanistic study exhibits that the reaction via multicomponent, one-pot, two-step incooperating three-components' reactants under nominal conditions efficiently synthesizes the intermediates in shorter than reported time along with the formation of a novel compound [5-amino-6-cyano-3-hydroxybenzo[c]coumarin] in the presence of Ni-Cu-Al-CO3 hydrotalcite as a heterogeneous catalyst. Hydrotalcite functions as an efficient and versatile catalyst as it is safe, easy to work up, and recyclable many times under ambient conditions, and the reaction time is shorter. The aforementioned conditions make these solid basic heterogeneous catalysts environmentally friendly. The product yield obtained was 89%. The product was characterized using FTIR, LCMS, and NMR. Electrochemical studies were also carried out to check the reduction and oxidation behavior. The synthesized product showed antimicrobial activity. Antimicrobial activity against human pathogens, viz, S. Aureus, P. Aeruginosa, and P. Bulgaria, was studied by using the agar well diffusion method. The molecular docking studies of 5-amino-6-cyano-3-hydroxybenzo[c]coumarin exhibit its suitable attachment at the active center of the type IIA topoisomerases and gyrase enzymes which suggest its potential antibacterial activity when compared using ciprofloxacin drug as the control.

Anti-malarial property of steroidal alkaloid conessine isolated from the bark of Holarrhena antidysenterica.

BACKGROUND: In the face of chronic and emerging resistance of parasites to currently available drugs and constant need for new anti-malarials, natural plant products have been the bastion of anti-malarials for thousands of years. Moreover natural plant products and their derivatives have traditionally been a common source of drugs, and represent more than 30% of the current pharmaceutical market. The present study shows evaluation of anti-malarial effects of compound conessine isolated from plant Holarrhena antidysenterica frequently used against malaria in the Garhwal region of north-west Himalaya. METHODS: In vitro anti-plasmodial activity of compound was assessed using schizont maturation and parasite lactate dehydrogenase (pLDH) assay. Cytotoxic activities of the examined compound were determined on L-6 cells of rat skeletal muscle myoblast. The four-day test for anti-malarial activity against a chloroquine-sensitive Plasmodium berghei NK65 strain in BALB/c mice was used for monitoring in vivo activity of compound. In liver and kidney function test, the activity of alkaline phosphatase (ALP) was examined by p-NPP method, bilirubin by Jendrassik and Grof method. The urea percentage was determined by modified Berthelot method and creatinine by alkaline picrate method in serum of mice using ENZOPAK/CHEMPAK reagent kits. RESULTS: Compound conessine showed in vitro anti-plasmodial activity with its IC50 value 1.9 µg/ml and 1.3 µg/ml using schizont maturation and pLDH assay respectively. The compound showed cytotoxity IC50= 14 µg/ml against L6 cells of rat skeletal muscle myoblast. The isolated compound from plant H. antidysenterica significantly reduced parasitaemia (at 10 mg/kg exhibited 88.95% parasite inhibition) in P. berghei-infected mice. Due to slightly toxic nature (cytotoxicity = 14), biochemical analysis (liver and kidney function test) of the serum from mice after administration of conessine were also observed. CONCLUSION: The present investigation demonstrates that the compound conessine exhibited substantial anti-malarial property. The isolated compound could be chemically modified to obtain a more potent chemical entity with improved characteristics against malaria.

Antiprotozoal activities of traditional medicinal plants from the Garhwal region of North West Himalaya, India.

ETHNOPHARMACOLOGICAL RELEVANCE: In a search for new plant-derived biologically active compounds against protozoan parasites, an ethnopharmacological study was carried out to evaluate extracts from selected 17 traditional medicinal plants which were used by healers from the Garhwal region of North West Himalaya for the treatment of protozoal infections and fever including malaria. MATERIALS AND METHODS: In vitro activity against erythrocytic stages of Plasmodium falciparum was determined using a modified [3H]-hypoxanthine incorporation assay with the chloroquine- and pyrimethamine-resistant K1 strain. Activity against Trypanosoma brucei rhodesiense was performed on the STIB 900 strain and activity against Trypanosoma cruzi on infected rat skeletal myoblasts (L6 cells) seeded in 96-well microtitre plates while amastigotes of Leishmania donovani strain MHOM/ET/67/L82 were used to assess activity against Leishmania donovani. Cytotoxicity assays were performed against rat skeletal myoblasts (L6-cells). RESULTS AND CONCLUSIONS: Extracts of Artemisia roxburghiana, Roylea cinerea, Leucas cephalotes, Nepeta hindostana and Viola canescens showed good antiplasmodial activity (IC50<5 µg/ml). The chloroform extract of Artemisia roxburghiana was the most active (IC50 value of 0.42 µg/ml) and the most selective (SI=78) extract for Plasmodium falciparum among all plants extracts examined. The chloroform extract of Leucas cephalotes and the petroleum ether extract of Viola canescens exhibited substantial activities against Leishmania donovani with IC50 values of 3.61 µg/ml (SI=8) and 0.40 µg/ml (SI=30), respectively. The petroleum ether extract of Viola canescens exhibited activity against Trypanosoma cruzi with an IC50 value of 1.86 µg/ml (SI=7). Methanol and water extracts from all plants under investigation were found inactive against all parasites tested. These results support investigation of components of traditional medicines as potential new antiprotozoal agents. On the other hand since herbalism has become the main stream throughout the world, investigation demonstrates that these non-polar plant extracts of six of the plants examined in this study could play an important role in herbal formulations for the treatment of vector borne protozoal diseases.

Anti-malarial activity of Holarrhena antidysenterica and Viola canescens, plants traditionally used against malaria in the Garhwal region of north-west Himalaya.

BACKGROUND: The increasing number of multidrug-resistant Plasmodium strains warrants exploration of new anti-malarials. Medicinal plant research has become more important, particularly after the development of Chinese anti-malarial drug artemisnin from Artemisia annua. The present study shows evaluation of anti-malarial effects of two plants commonly used against malaria in the Garhwal region of north-west Himalaya, in order to discover the herbal-based medicine. METHODS: In vitro anti-plasmodial sensitivity of plant extracts was assessed using schizont maturation and parasite lactate dehydrogenase (pLDH) assay. Cytotoxic activities of the examined extracts were determined on L-6 cells of rat skeletal muscle myoblast. The 4-day test for anti-malarial activity against a chloroquine sensitive Plasmodium berghei NK65 strain in Swiss albino mice was used for monitoring in vivo activity of plant extracts. RESULTS: Chloroform extract of H. antidysenterica (HA-2) and petroleum ether extract of V. canescens (VC-1) plants significantly reduced parasitaemia in P. berghei infected mice. The extract HA-2 showed in vitro anti-plasmodial activity with its IC50 value 5.5 µg/ml using pLDH assay and ED50 value 18.29 mg/kg in P. berghei infected Swiss albino mice. Similarly petroleum ether extract of V. canescens (VC-1) showed in vitro anti-plasmodial activity with its IC50 value 2.76 µg/ml using pLDH assay and ED50 15.8 mg/kg in P. berghei infected mice. The extracts coded as HA-2 at 30 mg/kg and VC-1 at 20 mg/kg exhibited parasite inhibition in mice: 73.2% and 63.0% respectively. Of these two plant extracts, petroleum ether extract of V. canescens was found slightly cytotoxic. CONCLUSION: The present investigation reflects the use of these traditional medicinal plants against malaria and these plants may work as potential source in the development of variety of herbal formulations for the treatment of malaria.