Current Bioactive Compounds - Volume 15, Issue 3, 2019

Background: Acquired immunodeficiency syndrome (AIDS) and cancer treatment have been a major task for research scientists and pharmaceutical industry for the last many years. Seeking to the development, many promising chemical entities especially five-membered heterocyclic rings like oxadiazole have revealed good anticancer and anti HIV activities. The current review enlists some recently developed anti-HIV and anti-cancer oxadiazole moieties. Methods: on the basis of structural modification for the syntheses of new oxadiazole analogs, the new anti-HIV and anti-cancer agents have been summarized, which can improve treatment of AIDs and cancer. Results: The oxadiazole ring is more potent in comparison to some other heterocyclic rings (five and six membered) towards anti-HIV and anti-cancer activities. The important mechanisms involved for anti HIV and anticancer activity are mainly inhibition of enzymes like protease, HIV-integrase, telomerase, histone deacetylase, methionine amino peptidase, thymidylate synthase and focal adhesion kinase and inhibition of some growth factors. Conclusion: By reviving the past literature about 50 most potent oxadiazole derivatives, depending upon activity and structural modifications, have been selected as potent anti-HIV, and anti-cancer agents. Thus, oxadiazole seems to be a ‘privileged structure’ for further screening and syntheses of the new drug analogs against life threatening HIV and cancer like diseases.

The aim of this literature review is to compile data of heterocyclic antigiardial agents. The importance is to analyze the structural requirements for improved antigiardial activity, to overcome resistance and enhance the bioavailability of the compounds under study. Though, nitroimidazoles/ imidazoles and benzimidazoles are major classes, other heterocyclic scaffolds viz. oxoindolinylidene, dioxodihydroisobenzofuran-5-carboxamide, fluoroquinolone, thieno[2,3-b]pyridine- 5-carbonitrile, α-amino-phosphonate analogs of polyoxins, nitazoxanide benzologue, thiazole and triazolyl- quinolone chalcone also possess activity against Giardia species. Heterocyclic phytoconstituents are also included to have a deep idea of antigiardial activity of herbs possessing heterocyclic constituents.

Background: Pyrimidine is the six membered heterocyclic aromatic compound similar to benzene and pyridine containing two nitrogen atoms at 1st and 3rd positions. Pyrimidine is present throughout nature in various forms and is the building blocks of numerous natural compounds from antibiotics to vitamins and liposacharides. The most commonly recognized pyrimidines are the bases of RNA and DNA, the most abundant being cytosine, thymine or uracil. Results: Pyrimidine is a core structure in a wide variety of compounds that exhibits significant biological activity and also plays an important role in the drug discovery process. Various synthetic aspects indicated that pyrimidine derivatives are easy to synthesize and has diverse biological and chemical applications. The present review article aims to review the work reported on synthesis, anticancer and antiviral potentials of pyrimidine derivatives during new millennium. Conclusion: It may be concluded that the fused pyrimidine derivatives enhanced the anticancer potential against different human cancer cell lines and antiviral potential against different human immunodeficiency virus (HIV), herpes simplex virus (HSV-1) etc, which created interest among the medicinal chemists in the pyrimidine skeleton in medicinal chemistry. Thus, a tremendous scope for research is present in this direction for investigating pyrimidine derivatives as lead molecules.

Background: Thiazole is widely investigated bioactive scaffold and dynamic tool in medicinal chemistry research. Significance of thiazole compounds are well documented as thiazole is an obligatory structure of number of currently available therapeutics. In spite of that, thiazole derivatives are endowed with myriad biological activities, such as antiviral, anticancer, antibacterial, antifungal, antimalarial, antiparkinsonian, anti-inflammatory activities and many more. Methods: In recent past, different approaches have been introduced for synthesis of thiazole and related compounds. Intrinsic molecular interaction between newly synthesized thiazole compounds and plethora of drug targets/enzymes has rendered discovery of new drug molecules with advances in modes of action. A renewed interest in therapeutic use of thiazole derivatives has been seen among the prospective researchers as exemplified by influx of huge scientific articles and patents. Some important patents of anti-infective and anticancer interest have been addressed appropriately and are presented in tables. Results: This review paper is a contemporary approach on therapeutic/applications of thiazole derivatives by summarizing important patents filed from 2000-2017. The main focus of these patents is on anti-infective and anticancer potential of thiazole based compounds. Conclusion: These approaches may provide valuable information for the further design of more active biological agents through various modifications and derivatizations.

Background: Heterocyclic compounds are an integral part of the chemical and life sciences and constitute a considerable quantum of the modern research that is being currently pursued throughout the world. Methods: This review was prepared by collecting the available literature reports on various databases and an extract was prepared for each report after thorough study and compiling the recent literature reports on heterocyclic amides from 2007 to 2018. Results: This review summarizes the bio-potential of heterocyclic amides as antimicrobial, anticancer, anti-tubercular and antimalarial agents which would be very promising in the field of medicinal chemistry. Conclusion: A wide variety of heterocyclic amides have already been reported and some are currently being used as active medicaments for the treatment of disease. Still, the research groups are focusing on the development of newer heterocyclic amide derivatives with better efficacy, potency and lesser side effects. This area has got the tremendous potential to come up with new chemical entities of medicinal importance.

Background: Trypanosomosis is an important disease of both humans and animals commonly found in most parts of Africa and South America. Because of their activities, the parasites produce numerous changes in the cellular and biochemical constituents of blood. Also, trypanosomosis cause immunosuppression and also induce lipid peroxidation in the host. Probiotics confer beneficial health benefit to the host such as immune stimulation, protection against pathogens, metabolism, reduced oxidative stress, etc. Methods: Thirty (30) adult albino rats were assigned into 5 groups (A – E) of 6 rats each. Groups A, B and C rats were fed feed supplemented with probiotics at 0.08, 0.12 and 0.16 mg per kg respectively. On day 14 on the supplementation (OTS), groups A, B, C and D rats were infected with 1 x 106 trypanosomes intraperitonealy. Group E served as the not infected, not supplemented control. Results: The pre-infection supplementation did not vary the serum alanine transaminase (ALT), aspartrate transaminase (AST), urea, creatinine and total protein values of groups A, B and C. However, following infection, the ALT value of group D (infected, not supplemented) was significantly (p<0.05) higher than other groups on day 42 OTS. Also, the AST value of groups A and D were significantly (p<0.05) higher than group E but not with groups B and C on days 42 and 56 on the supplementation. On day 28 OTS, the urea level of group B was significantly (p<0.05) lower than group D whereas on days 42 and 56, group E and groups E and C were significantly (p<0.05) lower than other groups respectively. The serum creatinine level showed increase following infection with groups A and D being significantly (p<0.05) higher than other groups on days 42 and 56 OTS. On day 28 OTS, the total protein value of group A was significantly (p<0.05) lower than group C but not with other groups. By days 42 and 56 OTS, group D showed significantly (p<0.05) lower protein level when compared with other groups. The mean parasitaemia level of group D was significantly higher than other infected infected groups on days 28 and 42 on the supplementation. However, on day 56, the parasitaemia level of all infected groups did not vary (p>0.05). Conclusion: The ability of the supplementation to keep serum biochemical values before infection within range, and the subsequent maintenance of the value during most part of the infection were indication that probiotic was not toxic and may play a vital role in management of trypanosomosis.

Background: Luteolin is a flavonoid unveiling various therapeutic activities, found in Vitex negundo L. Thus, there is a need to present process parameters at which maximum amount of luteolin can be extracted from V. negundo L. leaves in “one-run”. Objective: Response surface methodology (RSM) was employed for optimizing the process parameters for the extraction of luteolin from V. negundo L. leaves. The study also compared the efficacy of various traditional and modern extraction methods for luteolin extraction. Methods: Extraction conditions (solvent to drug ratio, extraction temperature and extraction time) were optimized by RSM, Box-Behnken Design (BBD). Quantification of luteolin in various extracts was done through High Performance Liquid Chromatography (HPLC). Results: Hot solvent extraction by reflux technique stood out to be the best technique and methanol was found to be the most effective solvent for luteolin extraction.Through the use of BBD, the optimal conditions for luteolin extraction were established as: solvent to drug ratio- 17.7 mL/g, extraction temperature- 55.5°C and extraction time-2.04 hours. Under such conditions 7.32 %w/w of luteolin was yielded which was close to predicted value of 7.29 %w/w. Conclusion: Reflux technique stood out to be the best among all the studied modes of extraction and methanol proved to be the most effective solvent. Moreover, all the three variables significantly affected the luteolin extraction. Our study shows the applicability of a statistical technique, RSM in phytocompound extraction field. This makes the optimization technique cheap and less laborious than the traditional optimization method.

Background: Amino acid based surfactants constitute an important class of surface active biomolecules showing remarkable biocompatible properties. Antimicrobial activity is one of the most remarkable biological properties of this kind of surfactants, which have been widely studied against a broad spectrum of microorganisms. However, the antifungal activity of this kind of compound has been less well investigated. The aim of this work is the study of the antifungal activity of two novel argininebased surfactants (Nα-benzoyl-arginine decylamide, Bz-Arg-NHC10 and Nα-benzoyl-arginine dodecylamide, Bz-Arg-NHC12), obtained by an enzymatic strategy, against phytopathogenic filamentous fungi and dermatophyte strains. Methods: Four phytopathogenic fungi (Fusarium oxysporum, Fusarium solani, Colletotrichum gloeosporioides and Colletotrichum lindemuthianum) and two human pathogenic fungi (dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes) were tested. Inhibition of vegetative growth and conidia germination was investigated for the phytopathogenic fungi. In order to elucidate the possible mechanism of biocide action, membrane integrity, as well as the production of reactive oxygen species (ROS) were evaluated. Additionally, the inhibition of germination of dermatophyte microconidia due to both arginine-based surfactants was studied. Minimum inhibitory concentration, as well as the concentration that inhibits 50% of germination were determined for both compounds and both fungal strains. Results: For the vegetative growth of phytopathogenic fungi, the most potent arginine-based compound was Bz-Arg-NHC10. All the tested compounds interfered with the conidia development of the studied species. Investigation of the possible mechanism of toxicity towards phytopathogenic fungi indicated direct damage of the plasma membrane and production of ROS. For the two strains of dermatophyte fungi tested, all the proved compounds showed similar fungistatic efficacy. Conclusion: Bz-Arg-NHC10 and Bz-Arg-NHC12 were demonstrated to have broad biocidal ability against the proliferative vegetative form and the asexual reproductive conidia. Results suggest that both membrane permeabilization and induction of oxidative stress are part of the antifungal mechanisms involved in the interruption of normal conidia development by Bz-Arg-NHCn, leading to cell death.

Background: In recent years, plant extracts are considered as an important source of many drug formulations for treatment of human beings from infection diseases. The objective of this study was to evaluate the antimicrobial activity of Salix mucronata leaves extracts and isolate their bioactive phytochemicals. Methods: The dry powder of Salix mucronata was extracted with different aqueous methanol concentrations. The 85% methanolic extract was further fractionated using different organic solvents. The antimicrobial activity of different extracts and fractions was evaluated. The most bioactive fractions were submitted for chromatographic isolation and structure elucidation of their phytochemicals using chromatographic and spectroscopic methods. Results: The ethyl acetate and the butanolic fractions derived from 85% MeOH extract gave a high antimicrobial activity with inhibition zones ranging between 10 mm and 26 mm and minimum inhibitory concentration (MIC) value of 8 mg/mL. While the butanolic fraction showed zones of inhibition ranging between 10 mm and 25 mm with MIC 8 mg/mL. Six compounds were isolated from ethyl acetate fraction and their structures were elucidated as; apigenin (1), quercetin (2), quercetrin (3), rhamnazin -3-O-β-D-glucopyranoside (4), Chrysoeriol-7-O-β-D-glucuronoid- 6 -methyl ester (5), and tremuloidin (6). Also, five compounds were isolated from the butanolic fraction and their structures were elucidated as; kaempferol (7), luteolin (8), luteolin-3 - methoxy-4 - O-β-D- glucopyranoside (9), isorhamnetin -3-O-β -D-glucopyranoside (10) and salicin (11). Conclusion: The results of the present study showed that the ethyl acetate and the butanolic fractions contain high flavonoids and salicinoids compounds which may attribute to their potential as antimicrobial agents.