Mini Reviews in Medicinal Chemistry - Volume 20, Issue 12, 2020

Dengue is a major health threat related to arbovirus and is endemic in more than 100 countries with an annual estimated above 390 million incidences of infection all around the world. During the period 1996-2015, a considerable increase in the number of dengue cases (more than 500%) was reported in India. Information about dengue disease burden, its prevalence, incidence and geographic distribution is critical in planning appropriate control measures against dengue fever. Till date, no specific treatment for dengue fever is available in any system of medicine, which can be accepted globally. Therefore, safe, cost-effective, and efficacious agents possessing anti-viral potential against dengue virus are needed to be searched in order to fight the dengue infection globally. The aim of the present review is to systematically revise the published research work available concerning the development and evaluation of some heterocyclic scaffolds in the management of dengue.

Studies regarding the uses and biological benefits curcumin have long been paid worldwide attention. Curcumin is a polyphenol found in the turmeric spice, which is derived from the rhizomes of Curcuma longa. Curcumin is a major constituent of the traditional Indian holistic system, Ayurveda, and it is well-known in treating diverse ailments. The aim of this study is to conduct an overview that introduces the traditional uses and therapeutic effects of this valuable phytochemical with more focus on the antitumor results. This review was conducted based on published articles on PubMed, Medline, and Web of Science databases. In this study, the search strategy identified 103 references. Curcumin is found to possess many functions in recent years. It is commonly used for its antioxidant, antimicrobial, anti-inflammatory, antitumor, anti-diabetic, hypolipidemic, hepatoprotective, and neuroprotective effects. Curcumin has been greatly reported to prevent many diseases through modulating several signaling pathways, and the molecular bases of its anti-tumor bioactivities are imputed to the antiproliferative, anti-inflammatory, pro-apoptotic, anti-angiogenesis and anti-metastasis effects. The antitoxic potential of curcumin against various toxin like Aflatoxin B1 is reported. Although curcumin is a safe and promising phytochemical, it suffers from bioavailability problems that limit its therapeutic efficacy. Thus, various promising strategies allowed for the achievement of multiple and effective varieties of curcumin formulations, such as adjuvants, nanoparticles, liposome, micelle and phospholipid complexes, metal complexes, derivatives, and analogues. In conclusion, curcumin is widely used for myriad therapeutic purposes that trigger its significant value. This short review aims to highlight the known biological activities of curcumin and provide evidence for its antitumor effects.

Since early times, various plants have been used as remedies for treating different kinds of diseases and lesions with satisfying results. The phenolic compounds are secondary metabolites from medicinal plants which include a wide category of compounds such as phenolic acids, flavonoids, tannins, stilbenes, curcuminoids, xanthones, coumarins, lignans, etc. Between these, lignans are considered important in cancer prevention and treatment, besides other beneficial health effects, e.g. antioxidant, anticarcinogenic, antimutagenic, and anti-estrogenic effects. This review summarizes the most recent literature and the most important results concerning plant lignans and their derivatives in cancer prevention and treatment, both in vitro and in vivo assessments. The mechanistic aspects will be also highlighted.

This article provides comprehensive and collective facts about teneligliptin. Teneligliptin is a dipeptide peptidase-4 (DPP-4) inhibitor that belongs to the third generation, used in the management of type 2 diabetes. It inhibits human DPP-4 enzyme activity. This drug falls under class 3; it interacts with S1, S2, and S2E extensive sub-sites. Teneligliptin and its metabolites are mainly determined in the human plasma matrix by hyphenated chromatographic methods. These developed methods could be foreseen for their clinical applications. Moreover, the stress degradation studies of Teneligliptin under different stress conditions provide an insight into degradation pathways and help in the elucidation of the structure of the degradation products by liquid mass spectroscopy. These methods are also used for routine quality control analysis of teneligliptin in pharmaceutical dosage forms.

Withanolides are a group of highly oxygenated steroids derived from a C28 ergostane skeleton, and have attracted significant scientific interest due to their complex structural features and multiple bioactivities. More than 170 new natural withanolides were isolated and identified in the last 5 years. This review provides a comprehensive summary of the structural, biological and pharmacological activities of these new compounds.

Schistosomiasis is a chronic parasitic disease caused by a trematode blood fluke of the genus Schistosoma that belongs to the Schistosomatidae family. It is a neglected disease in different regions of Asia. In this review, 218 articles (between 2000 and 2017) related to the topic were collected from PubMed and Google scholar and reviewed. After thoroughly reading collected articles, due to irrelevant topic requirements, 94 articles were excluded. Articles that have data associated with Asian regions are considered. In Asia, the disease is prevalent in China, Philippines, Indonesia, Yemen, Nepal and Laos, etc. While in Pakistan, India and Bangladesh, the disease is not endemic and very few cases were reported. The disease was eliminated from Japan and Iran. The current review highlights the geographical distribution among Asian countries, transmission patterns, diagnosis, control strategies based on the use of anthelmintic plants and management practices implemented in Asia for the control of schistosomiasis. However, new implementations to treat schistosomiasis in humans should be proved to eliminate the disease finally in the future. This review emphasizes the biological control of schistosomiasis for the eradication of the disease from Asia in the near future.

Urothelial carcinoma of the bladder (UCB) is a very heterogeneous disease and divided into invasive and non-invasive disease. In non-muscle-invasive bladder cancer (NMIBC), recurrence after transurethral resection or instillation-therapy, and progression to invasive disease are issues of concern. In muscle-invasive bladder cancer (MIBC), systemic recurrence after radical treatment is a pressing problem, as the available therapies in this setting are of limited efficacy. For both entities there are only few clinicopathological prognostic biomarkers to identify subgroups at risk to aid in decision making to whom to offer early radical cystectomy in case of NMIBC or neoadjuvant/adjuvant chemotherapy in case of MIBC to improve outcomes. Despite advances in surgery and intravesical therapy, up to 30% of NMIBC-patients suffer progression to MIBC. After cystectomy around 50% of MIBC patients suffer local or systemic recurrence and subsequently succumb to the disease. Standard features, like pathological staging and grading, are not sufficient to identify patients at risk beyond doubt. Recent advances in molecular diagnostics in combination with standard pathological features could be used to improve risk stratification of patients, guide treatment plans and ultimately improve outcomes. Immunohistochemical (IHC) analysis can detect altered regulatory pathway-products. Until now a plethora of prognostic IHC-biomarkers has been reported on in UCB, but only few have been validated and no biomarker is in routine use or recommended by guidelines. In this review we discuss the prognostic potential of the most promising IHC-biomarkers in NMIBC and MIBC with a focus on prognostication of recurrence and stage progression in NMIBC as well as recurrence-free, cancer-specific and overall survival in MIBC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Chemoresistance remains the major factor for limited efficacy of the HCC treatment. Thus, exploring the mechanisms underlying drug resistance is of great importance. Secretory clusterin (sCLU), a stressactivated and ATP-independent molecular chaperone, is up-regulated in numerous tumors and correlated with malignant phenotypes. For HCC, the implication of sCLU was previously addressed in tumor growth, metastasis, as well as early diagnosis and poor prognosis. Notably, accumulating studies have emphasized its vital role in drug resistance of HCC. Depletion of sCLU synergistically could enhance the sensitivity of HCC cells to a variety of chemotherapy agents. Herein, we summarized the potential mechanisms accounting for the sCLU-induced chemoresistance, including promoting apoptosis evasion, facilitating epithelial-mesenchymal transition (EMT), maintaining the viability of cancer stem cell (CSC), enhancing drug efflux capacity, and regulating autophagic activities. The current evidence suggest that targeting sCLU might be a promising approach in overcoming chemoresistance of HCC.

Objective: Coupling of ethyl 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetate 2 with diazotized anilines in ethanol in the presence of sodium acetate yielded 2-(2-arylhydrazono)-2-(6,7- dimethoxy-3,4-dihydroisoquinolin-1-yl)acetate (4a-f). Methods: Treatment of 2 with α-bromoketones 6a-f in dry benzene at reflux gave the corresponding isoquinolinium bromides 7a-f. Refluxing of each of the salts 7a-f in dry benzene and in the presence of triethylamine yielded 2-arylpyrrolo-[2,1-a]isoquinoline structures 8a-f, that converted to ethyl (E)-8,9- dimethoxy-3-(phenyldiazen-yl)-2-(aryl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-1-carboxylate (9a-f) upon treatment with diazotized anilines 3 in ethanol in the presence of sodium acetate. Results and Conclusion: Cytotoxic assay was performed for in vitro antitumor screening against caucasian breast adenocarcinoma (MCF7), hepatocellular carcinoma (HepG2) and colorectal carcinoma (HCT-116) cell lines. The results were compared with the standard anticancer drug (doxorubicin). Molecular docking using MOE 2014.09 software was carried out for the most potent compound 4d, which showed the highest binding affinity towards the four tested proteins and thus initiated apoptosis of cancer cells.

Background: The accurate ranking of analogs of lead molecules with respect to their estimated binding free energies to drug targets remains highly challenging in molecular docking due to small relative differences in their free energy values. Methods: Free energy perturbation (FEP) method, which provides the most accurate relative binding free energy values were earlier used to calculate free energies of many ligands for several important drug targets including Fructose-1,6-BisphosPhatase (FBPase). The availability of abundant structural and experimental binding affinity data for FBPase inhibitors provided an ideal system to evaluate four widely used docking programs, AutoDock, Glide, GOLD and SurflexDock, distinct from earlier comparative evaluation studies. Results: The analyses suggested that, considering various parameters such as docking pose, scoring and ranking accuracy, sensitivity analysis and newly introduced relative ranking score, Glide provided reasonably consistent results in all respects for the system studied in the present work. Whereas GOLD and AutoDock also demonstrated better performance, AutoDock results were found to be significantly superior in terms of scoring accuracy compared to the rest. Conclusion: Present analysis serves as a useful guide for researchers working in the field of lead optimization and for developers in upgradation of the docking programs.