Current Bioactive Compounds - Volume 16, Issue 1, 2020

Background: Fever, is known as pyrexia, may occur due to infection, inflammation, or any tissue damage and disease states. Normally, the infected or damaged tissue initiates the enhanced formation of pro-inflammatory mediators like cytokines which further increases the synthesis of prostaglandin E2 (PgE2) near the hypothalamic area and thereby trigger the hypothalamus to elevate the body temperature. Objective: Antipyretics are the agents which reduce the elevated body temperature. The most commonly used antipyretic agent, paracetamol, may be fatal due to its side effects. Methods: In this review paper, Chemical Abstracts, Google Scholar, PubMed, and Science Direct were the sources for the published article to collect information regarding antipyretic activity. Results: This review compiles the antipyretic plants that may be useful to treat fever due to various diseases. Conclusion: These medicinal plants could be good alternatives for traditional allopathic antipyretics.

Background: Tuberculosis, an infectious disease caused mainly by the Mycobacterium tuberculosis accounts for the highest number of deaths worldwide. Despite curing millions, the currently used drug regimens are bounded by various limitations such as long course of therapy, emergence of resistance and permanent tissue damage. The treatment of multidrug-resistant and extremely drugresistant tuberculosis is a challenging task due to its reliance on second-line drugs which are less potent and more toxic than those used in the clinical management of drug-susceptible tuberculosis. Therefore, the major challenges in the upcoming years are to overcome the emergence of increased number of multidrug-resistant as well as extensively drug-resistant strains and the ineptness of the current treatment regimens against latent tuberculosis. Bedaquiline and Delamanid are the only new anti-TB drugs that have been currently approved since more than 40 years after discovery of isoniazid. Bedaquiline is the first diarylquinoline derivative that has showed resilient culture conversion at 24 weeks in phase IIb trials. Methods: Extensive literature search on the topic was undergone using a focused question. Results: Fifty-eight research articles from journals of repute are included in the review. The vaccine and peptide-based conjugates are recent developments against Mycobacterium for selective and specific targeting to the desired tissues. Conclusion: In this review, we have focused on the different classes of chemical as well as plant based compounds as potent antitubercular agents against multidrug-resistant tuberculosis strains. This review falls light on the importance of research been undergoing in different parts of the world to combat the ever increasing problem of mycobacterial resistance and the various treatment options available for the treatment of tuberculosis.

Background: Piper betle Linn. (Piperaceae) is commonly known as “Green gold of India” due to its high commercial value. It is a Vedic plant used in various traditional system of medicine v.iz. Ayurveda system of medicine, Yunani system of medicine attributed to various pharmacological activities v.i.z. antioxidant, anti-inflammatory, analgesic, anti-fertility, antimutagenic etc. Objectives: The main objective of the present study is quantitative estimation of the various bioactive compounds present in leaf of P. betle L. (Bangla variety) by GC-MS analysis using head space method. Materials and Methods: The vapor sample of leaf of P. betle L. was prepared by head space method for GCMS analysis. GCMS analysis was carried out using high resolution Thermo scientific TSQ 8000 Gas Chromatograph-Mass Spectrometer. Helium is used as carrier gas (99.999 %) with a constant flow rate of 1 ml/min. Total run time was 29.10 min. Results: GC-MS analysis revealed the presence of 16 bioactive compounds in leaf of P. betle L. Eugenol (29.13%), Bakuchiol (11.79%) and α-linalool (14.88%) are the chief bioactive compounds of leaf. Leaf has been also reported to contain a good percentage of various terpenoids like β- caryophyllene (7.69), α-muurolene (4.19), α-bisabolene (0.98), etc. Conclusion: From GC-MS analysis results it can be concluded that leaf of P. betle L. is a reservoir of valuable phenolic and susquiterpene compounds. Eugenol chief biomarker compound present leaf is a versatile remarkable molecule. Due to number of phytoconstituents P. betle L. leaf is recommended as plant of phytopharmaceutical importance.

Background: Ficus glomerata (F. glomerata) Linn. Family Moraceace is a large tree found all over India including outer Himalayan ranges, Punjab, Chota Nagpur, Bihar, Orissa, West Bengal, Rajasthan, Deccan and also as a common plant in South India. It is planted around the home and temples. It is cultivated throughout the year, distributed in evergreen forests and moist localities. Objective: The Ethanolic Extract of roots of F. Glomerata (EEFG) belonging to the family Moraceace, was investigated for its antidiabetic activity using alloxan induced diabetic rats. Methods: Thirty rats were divided into 5 groups having 6 rats in each group. The alloxan was administered to the rats of all groups except normal control group through intraperitoneal route at a concentration of 140mg/kg body weight. A dose of 100mg/kg and 200 mg/kg body weight of EEFG was administered to alloxan induced diabetic rats. The administration of the extract was lasted for 11 days. Effectiveness of the extract on glucose, cholesterol, triglycerides, and high density lipoprotein and protein concentrations was analyzed. Results: Significant (p<0.05) reduction in the levels of glucose, cholesterol, triglyceride of the diabetic rats was observed after treatment with ethanolic extract. After subjecting to oral glucose tolerance test EEFG also showed significant improvement in glucose tolerance. Conclusion: F. glomerata root ethanolic extract showed that it possesses antidiabetic effect and can be found useful for the management of diabetes mellitus.

Background: Ficus glomerata Roxb. is a moderate-sized avenue tree distributed throughout India both as wild or cultivated. It is traditionally used in various traditional systems of medicine including Ayurveda, Siddha and Homoeopathy. In these indigenous systems of medicine, different parts of the plant Ficus glomerata are commonly used for the treatment of dysentery, diarrhea, diabetes, bilious affections, stomachache, menorrhage, haemoptysis and also as a carminative and astringent. Objectives:The current investigation deals with detail pharmacognostical studies on roots of Ficus racemosa mainly focusing the morphological, macroscopical analysis, prelimilnary examinations of root powder and florescence analysis. Methods: Physicochemical constants of roots of Ficus glomerata were estimated as per official guidelines. Results: Significant in vitro antioxidant activity was observed for alcoholic root extract of Ficus glomerata. The alcoholic extract and aqueous extract show the presence of tannins and saponins as major constituents. Remaining constituents were found to be carbohydrate, glycosides, phenolic compounds, gum and mucilage. Conclusion: Ficus glomerata possess significant antioxidant activities.

Background: Tryptamine, a biogenic monoamine that is present in trace levels in the mammalian central nervous system, has probable roles as a neurotransmitter and/or a neuromodulator and may be associated with various neuropsychiatric disorders. One of the ways tryptamine may affect the body is by the competitive inhibition of the attachment of tryptophan to tryptophanyl tRNA synthetases. Methods: This study has explored the effects of tryptamine on growth of six yeast species (Saccharomyces cerevisiae, Candida glabrata, C. krusei, C. dubliniensis, C. tropicalis and C. lusitaniae) in media with glucose or ethanol as the carbon source, as well as recovery of growth inhibition by the addition of tryptophan. Results: Tryptamine was found to have an inhibitory effect on respiratory growth of all yeast species when grown with ethanol as the carbon source. Tryptamine also inhibited fermentative growth of Saccharomyces cerevisiae, C. krusei and C. tropicalis with glucose as the carbon source. In most cases the inhibitory effects were reduced by added tryptophan. Conclusion: The results obtained in this study are consistent with tryptamine competing with tryptophan to bind mitochondrial and cytoplasmic tryptophanyl tRNA synthetases in yeast: effects on mitochondrial and cytoplasmic protein synthesis can be studied as a function of growth with glucose or ethanol as a carbon source. Of the yeast species tested, there is variation in the sensitivity to tryptamine and the rescue by tryptophan. The current study suggests appropriate yeast strains and approaches for further studies.

Background: There is a general lack of effective and economical chemotherapeutic agents for the treatment of widely prevalent leishmanias. To develop locally available, low cost alternative therapy, a series of diterpene lactones isolated from Suregada multiflora and their semisynthetic derivatives have been evaluated against the protozoan parasite Leishmania. Methods: A series of diterpene lactones were isolated from methanolic extract of Suregada multiflora. Major constituents were further derivatized through chemical and microbial transformations. Antileishmanial activity of structurally diverse diterpene lactones was performed by testing them in vitro against L. donovani promastigotes. All compounds were also tested for their cytotoxic effects by the brine shrimp bioassay. Results: Among all compounds evaluated in current studies, natural diterpenes Gelomulide A (1) and G (2) were found significantly active with IC50 values below 20μg/ml. While, among synthesized derivatives; compounds 5, 9 and 10 were found more potent with IC50 value 17.49, 18.38 and 17.81μg/ml, respectively. None of these compounds showed cytotoxic effects in the brine shrimp bioassay (LC50> 300). Conclusion: A new class of diterpene lactones was identified as potential antileshmanial agent. The structural diversity of natural and semisynthetic diterpene lactones, helped to rationalize structure– activity relationships. Activity of these diterpene lactones owed to C-8/14 epoxide along with unsubstituted C-1. Keto group at C-1 always lower the activity unless it is in α, β-unsaturated form. Presence of acetyl group at C-3 and 6 usually augmented the antileishmanila potential.

Background: Chitin is the main component of fungal, protozoan and helminth cell wall. They help to maintain the structural and functional characteristics of these organisms. The chitin wall is dynamic and is repaired, rearranged and synthesized as the cells develop. Active synthesis can be noticed during cytokinesis, laying of primary septum, maintenance of lateral cell wall integrity and hyphal tip growth. Chitin synthesis involves coordinated action of two enzymes namely, chitin synthase (that lays new cell wall) and chitinase (that removes the older ones). Since chitin synthase is conserved in different eukaryotic microorganisms that can be a ‘soft target’ for inhibition with small molecules. When chitin synthase is inhibited, it leads to the loss of viability of cells owing to the self- disruption of the cell wall by existing chitinase. Methods: In the described study, small molecules from plant sources were screened for their ability to interfere with hyphal tip growth, by employing Hyphal Tip Burst assay (HTB). Aspergillus niger was used as the model organism. The specific role of these small molecules in interfering with chitin synthesis was established with an in-vitro method. The enzyme required was isolated from Aspergillus niger and its activity was deduced through a novel method involving non-radioactively labelled substrate. The activity of the potential lead molecules were also checked against Candida albicans and Caenorhabditis elegans. The latter was adopted as a surrogate for the pathogenic helminths as it shares similarity with regard to cell wall structure and biochemistry. Moreover, it is widely studied and the methodologies are well established. Results: Out of the 11 compounds and extracts screened, 8 were found to be prospective. They were also found to be effective against Candida albicans and Caenorhabditis elegans. Conclusion: Purified Methyl Ethyl Ketone (MEK) Fraction1 (F1) of Coconut (Cocos nucifera) Shell Extract (COSE) was found to be more effective against Candida albicans with an IC50 value of 3.04 μg/mL and on L4 stage of Caenorhabditis elegans with an IC50 of 77.8 μg/mL.

Background: Tuberculosis is a catastrophe sprawled across the world. The World Health Organization Global Tuberculosis Report 2017 inferred that there were an estimated 10.4 million people suffered from tuberculosis including 490000 Multidrug-Resistant TB (MDR-TB) cases. Several new lead molecules like dinitrobenzamide derivatives were found to be highly active against multidrugresistant strains of M. tuberculosis. To further explore the pharmacophoric space around the dinitobenzamide moiety, a series of compounds have been synthesized by linking it with the thiazolidin- 4-one. The presented work is an effort to study the biological effect of thiazolidin-4-one scaffold on dinitrobenzamide derivatives as antitubercular agents. A molecular modeling study was also performed on the synthesized molecules to reveal the requirements for further lead optimization. Methods: The thiazolidin-4-one linked 3,5-dinitrobenzamide derivatives have been synthesized by onepot three-component condensation reaction of an amine, substituted aldehydes and thioglycolic acid in presence of N, N'-Dicyclohexylcarbodiimide (DCC). These compounds were evaluated against Mycobacterium tuberculosis H37Ra. A pharmacophore modeling approach has been used in order to explore the collection of possible pharmacophore queries of thiazolidin-4-one linked 3, 5-dinitrobenzamide derivatives against M. tuberculosis. The synthesized compounds were docked on to the M. tuberculosis DprE1 enzyme to identify the structural features requirement of these analogs against this potential target of M. tuberculosis. Results: The synthesized compounds showed the antitubercular activity in the range of 6.25-50 μg/ml. The pharmacophore modeling suggests that the presence of aromatic moiety, thiazolidin-4-one ring and one of the nitro groups are significant for inhibiting the enzymatic activity. While docking studies showed that hydrophobic and hydrogen bond interactions of the aromatic moiety and nitro group crucial to inactivate the DprE1 enzyme. Conclusion: The study showed that the linking of thiazolidin-4-one with dinitrobenzamide leads to compounds active against M. tuberculosis. These findings also suggested that further lead optimization would be carried out by focusing on the aromatic system along with electron-rich substituents placed on the thiazolidin-4-one for making better hydrophobic and hydrogen bond interactions with the DprE1 target.

Objectives: In this study, cytotoxic effect, anticholinesterase, hemolytic and antibacterial activities of crude extracts (petroleum ether, ethyl acetate and n-butanol) obtained from the plant Scabiosa stellata L. were evaluated. Methods: The cytotoxicity of extracts was tested by Brine shrimp lethality method; the acetylcholinesterase inhibitory activity was performed using Ellman's colorimetric method and the hemolytic activity was assessed by spectrophotometric method towards human erythrocytes. Furthermore, the antibacterial activity was estimated by agar disk diffusion assay against ten bacterial strains. Results: The phytochemical screening of the extracts revealed the presence of several types of secondary metabolites. A significant cytotoxic effect was observed for the n-butanolic extract with 57.2 ± 0.2 % of mortality at 80 μg/mL, the ethyl acetate extract had a moderate anticholinesterase activity at 200 μg/mL. The hemolytic assay exhibited that n-butanolic and ethyl acetate extracts induce hemolysis in dose-dependent manner with values of EC50 at 37.3 ± 0.5 and 106.6 ± 0.3 μg/mL, respectively. All the crude extracts showed antibacterial activity against most tested strains, with zones of inhibition ranging from 9 to 20 mm. Conclusion: The results indicate that the extracts obtained from S. stellata can be an important source of therapeutic agents against pathological damage due to free radicals inducing neurodegenerative and infectious diseases, while n-butanolic extract could be used as a good source of alternative natural antiproliferative compounds.

Background: Class II hydrophobin HFBII is a fungal protein with potential applications in pharmaceutical industry. Nevertheless, the antitumor activity of this protein has not been reported. Methods: In this study, natural type of Trichoderma reesei was cultivated in a submerged bioreactor to produce hydrophobin HFBII. The protein was purified using a reversed phase liquid chromatography, verified by MALDI-TOF, and then examined for its anticancer activity against T47D breast tumor cell line. Results: Different concentrations of hydrophobin HFBII from 1 nM to 500 μM were examined for this experiment. Hydrophobin HFBII with molecular weights of 7.0-7.2 kDa was achieved. The results of MTT assay showed that from the concentration of 100 μM and upwards, hydrophobin HFBII adversely affected the viability of the breast tumor cells. The IC50 value was reported to be 131 μM. Class II hydrophobin seems to be a very effective carrier for antitumor agent. Conclusion: This is the first report of HFBII cytotoxicity. However, there is lack of information regarding HFBII’s mechanism of action in cell death induction. Since, HFBII could play important roles in biomedicine, whether as a drug or a carrier for various kinds of pharmaceuticals, it is strongly suggested that its biological effects would be evaluated in detail.

Background: Bleomycin (BLM) is known to cause DNA damage in the Alveolar Epithelial Cells (AECs). It is reported that BLM is involved in the up-regulation of inflammatory molecules such as neutrophils, macrophages, chemokines and cytokines. The complex underlying mechanism for inflammation mediated progression of lung injury is still unclear. This investigation was designed to understand the molecular mechanisms associated with p53 mediated modulation of Plasminogen Activator Inhibitor-I (PAI-I) expression and its regulation by nano-curcumin formulation. Methods: A549 cells were treated with BLM to cause the cellular damage in vitro and commercially available nano-curcumin formulation was used as an intervention. Cytotoxic effect of nano-curcumin was analyzed using Methyl Thiazolyl Tetrazolium (MTT) assay. Protein expressions were analyzed using western blot to evaluate the p53 mediated changes in PAI-I expression. Results: Nano-curcumin showed cytotoxicity up to 88.5 % at a concentration of 20 μg/ml after 48 h of treatment. BLM exposure to the cells activated the phosphorylation of p53, which in turn increased PAII expression. Nano-curcumin treatment showed a protective role against phosphorylation of p53 and PAI-I expression, which in turn regulated the fibro-proliferative phase of injury induced by bleomycin. Conclusion: Nano-curcumin could be used as an effective intervention to regulate the severity of lung injury, apoptosis of AECs and fibro-proliferation during pulmonary injury.

Background: Parkinson's Disease results from a loss of dopaminergic neurons, and reduced levels of the neurotransmitter dopamine. Parkinson's Disease treatments involve increasing dopamine levels through administration of L-DOPA, which can cross the blood brain barrier and be converted to dopamine in the brain. The toxicity of dopamine has previously studied but there has been little study of L-DOPA toxicity. Methods: We have compared the toxicity of dopamine and L-DOPA in the yeasts, Saccharomyces cerevisiae and Candida glabrata by cell viability assays, measuring colony forming units. Results: L-DOPA and dopamine caused time-dependent cell killing in Candida glabrata while only dopamine caused such effects in Saccharomyces cerevisiae. The toxicity of L-DOPA is much lower than dopamine. Conclusion: Candida glabrata exhibits high sensitivity to L-DOPA and may have advantages for studying the cytotoxicity of L-DOPA.