Current Bioactive Compounds - Volume 17, Issue 1, 2021

Among the various fused heterocyclic rings, benzothiazole and its analogs have been explored broadly in search of newer therapeutic medicinal agents. The benzothiazole scaffold has been associated with huge biological potential like anticancer, antidiabetic, anti-inflammatory, antitubercular, antiviral, anti-convulsant etc. The occurrence of benzothiazole core in various compounds proves its value in the sphere of pharmaceutical chemistry. The connected research and developments in benzothiazole based chemistry become an active topic for medicinal scientists. A large number of benzothiazole and its heterocyclic derivatives are available in the market and used for the treatment as clinical drugs have been extensively used in practice to treat diverse types of ailments with high therapeutic potential. This review presents the latest therapeutic developments of benzothiazole containing compounds in the medicinal chemistry.

Background: In the last two decades, the flavonoids containing fused heterocyclic nucleus in their chemical structure have emerged to display a variety of pharmacological effects including antiallergic and anti-inflammatory the most recent to the list. These polyphenolic compounds exert their pharmacological effect by various mechanisms including inhibition of human neutrophil elastase, cytokines (Interleukins- IL-3 and IL-4) and mast cells. Methods: We adopted a structured search of notorious journal publication websites and electronic databases such as Science Direct, Bentham, Scopus, PubMed, Nature, Springer etc. for the collection of peer-reviewed research and review articles for the present review. The quality papers (109) were retrieved, studied, categorized into different sections, analyzed and used for article writing. Results: The backbone of this review article is based on four review articles of natural phenolics. Seventeen papers out of total one hundred and nine were about Quercetin the main molecule of interest, five papers outlined the potential benefits of Pycnogenol, Rutin was discussed in detail by considering eight papers in mind, Kaempferol which can be considered as a candidate of interest was referred from six articles. Conclusion: This review identified the Quercetin, Pycnogenol, Rutin and Kampferol as few bioflavonols out of hundreds of other compounds still under clinical trials that have been studied most. Marketed formulations of Pycnogenol are also available as nutraceuticals. These flavonoids have been also reported to the other pharmacological effects like anti-cancer, anti-oxidants, anti-hypertensive, antiviral, anti-ulcerogenic, anti-platelet, anti-hypotensive and anti-hepatotoxic. With all these versatile properties heterocyclic containing flavonoids may be a powerful candidate for the discovery of their utilization in other ailments like asthma.

The search for new drugs to treat viral infections and immune deficiencies of various etiologies is still one of the most important tasks of medicinal chemistry, pharmacy, and medicine due to the widespread prevalence of a number of socially dangerous viral infections. This review focuses on the chemical modification of Glycyrrhizic acid (Gl), the main component of licorice root, which is currently a leading natural glycoside that is considered to be promising for the development of new antiviral agents. The review presents the results of studies conducted over the past 15 years to obtain a library of Gl acid derivatives for biological studies and to search for leader compounds. The synthesis of new biologically active derivatives and analogues (conjugates with amino acids and dipeptides, amino sugars, licorice triterpene acids conjugates with amino sugars, saponins and mono glycosides, and heterocyclic amides) was conducted, and their antiviral and immune modulating properties were studied. Potent inhibitors of HIV, SARS CoV, Epstein-Barr, and influenza A/H1N1 viruses and the stimulators of primary immune response were found among the Gl derivatives and analogues that were produced.

Background: Histone Deacetylase (HDAC) inhibitors are a new class of therapeutic compounds that show promising results in a series of preclinical and clinical anticancer studies. Hydroxamic acids belong to one of the most significant classes of HDAC inhibitors. The member vorinostat (SAHA) was approved by the U.S. Food and Drug Administration for the treatment of cutaneous T-cell lymphoma. Methods: A series of eight novel hydroxamic acids containing 2-imidazolylphenyl(oxy/thio) alkanoic fragment designed to target Histone Deacetylase (HDAC) were synthesized in five steps from easily accessible 2(3H)-benzoxazolones and 2(3H)-benzthiazolones. The newly synthesized compounds were characterized by ¹H, ¹³C NMR, and elemental analysis. Results: The structure-activity relationship was examined via linker length alternation and variation of the heteroatom (oxygen or sulfur) and chlorine substitution pattern of the starting materials. The compounds were tested for their cytotoxic activity against two human cancer cell lines (HT-29 and MDA-MB-231). Our data indicate that the compound 6.1d is active in the micromolar range with IC50 of 9.7 μM for MDA-MB-231 cells. DNA fragmentation analysis of the most active compounds confirmed that apoptosis could be one of the mechanisms involved in cell death. Conclusion: Taken together, the results revealed that 6d may become a promising lead compound for new anticancer drugs discovery.

Background: Acne is caused by several factors, including the active secretion of sebaceous sweat glands, hyperkeratosis in the hair infundibulum and the effects of bacteria. One plant which has the potential as an antibacterial agent is the extract of Arum Manis mango leaves. Methods: The Minimum Inhibitory Concentration (MIC) of methanol extract of mango leaves was determined, which can inhibit Propionibacterium acnes activity. The antibacterial activity tests were performed using agar diffusion. The ointment formulation, the characteristics of ointment preparations, and the ointment activity against P. Acnes are discussed. Results: MIC of methanol extract of mango leaves value is 5 ppm with an inhibition zone of 1 mm. The ointment obtained is white, has a distinctive smell, semisolid form, possesses a pH of 4.92 - 5.87, dispersive power of 5.05 - 6.30 cm, and adhesive power of 1 - 3.67 seconds, homogeneous and protective. Ointment preparations of methanol extract of mango leaves have activity on P. acnes on the 0 and 15th day of storage. The activities of ointment preparation on day 0 with concentrations of 0, 5, 10 and 15 ppm are 0.00 mm; 10.20 mm; 19.97 mm and 23.60 mm respectively, while the inhibition zones produced by the preparation of ointment on day 15 with concentrations of 0, 5, 10 and 15 ppm are 0.00 mm; 5.71 mm; 9.58 mm and 21.88 mm respectively. Conclusion: Methanol extract of mango leaves (Mangifera indica L.) and ointment preparation can inhibit the growth of Propionibacterium acnes.

Background: Alcohol withdrawal syndrome leads to irritability, aggressiveness, body posture and motor abnormalities, sensory hyper reactivity and changes in various enzyme levels. Dhatryadi ghrita penetrates the blood-brain barrier to decrease the cravings for alcohol in this syndrome. Objective: To evaluate the effect of alcoholic extract of Dhatryadi ghrita on alcohol withdrawal syndrome in Wistar rats. Materials & Methods: A liquid diet with 7.2%, v/v ethanol was administered to the Wistar rats for 21 days. Control group animals received saline and normal diet. After alcohol withdrawal, rats were examined at 6th and 24th hour for anxiety and hyper locomotor activity as major withdrawal signs. Anxiety due to ethanol withdrawal was tested with the help of elevated plus maze, light and dark models. The hyper locomotor activity was assessed using Actophotometer. The hepatic enzymes level was determined with the help of the Bio-chemical Analyzer. ghrita extracts (100, 200,300 mg/kg, oral) were administered to different groups and diazepam as standard (2 mg/kg, i.p) was administered to the treatment group animals 30 minutes before alcohol withdrawal estimation. Drug treatment was administered 30 minutes before the second observation at the 24th hour. Results: Findings from the present study revealed that Ghrita extract treatment at doses 100, 200 and 300 mg/kg, oral in ethanol-dependent rats had a significant protective effect on signs and symptoms of ethanol withdrawal in alcohol-dependent rats. Conclusion: Dhatryadi extract acts effectively for the treatment of alcohol abstinence syndrome. The extract treatment has beneficial effects on ethanol withdrawal depressive-like behavior in rats.

Background: Saussurea lappa is a traditionally well-known plant appreciated for its biological activities and medicinal uses. Objective: In the present study, the recovery of antioxidants from Saussurea lappa was optimized using Response Surface Methodology (RSM). The efficiency of a newly-patented Infrared (IR) technology, Ired-Irrad®, was compared to that of the emerging ultrasound method (US) and the conventional solid liquid Water Bath (WB) extraction. Methods: The effects of time (t) and Temperature (T), mostly known to affect the extraction process, were tested on maximizing the Total Phenolic compounds Concentration (TPC) and the radical scavenging activity (AA). Response surface methodology was used for the optimization process. Results: A multiple response optimization of both time (t) and Temperature (T) was conducted, showing the best extraction conditions to be for WB: t= 43.86 min, T=33.79°C, for US: t= 65.47 min, T= 57.97°C and for IR: t= 42.5 min, T=34.19°C. The quantity of the optimally extracted polyphenols by WB, US and IR; as well as many of their bioactivities were compared. IR extraction gave the highest yield of TPC (15.3 mg GAE/g DM) followed by US (14.8 mg GAE/g DM) and lastly WB (13.9 mg GAE/g DM). The highest antioxidant and antiradical activities were also obtained by the IR treatment. The optimal IR extract inhibited the growth of Staphylococcus aureus and Escherichia coli up to 65 and 35%, respectively. Moreover, all Saussurea lappa extracts (WB, US and IR) inhibited up to 96% the production of Aflatoxin B1 (AFB1) by Aspergillus flavus. Conclusion: Our findings on the extraction of antioxidants from Saussurea lappa demonstrated that IR technology is an efficient novel method that can be used to extract the maximum yield of polyphenols, with the highest antioxidant, antiradical and antibacterial activities.