Current Medicinal Chemistry - Volume 27, Issue 40, 2020

As a major neurodevelopmental disorder, Autism Spectrum Disorder (ASD) encompasses deficits in communication and repetitive and restricted interests or behaviors in childhood and adolescence. Its etiology may come from either a genetic, epigenetic, neurological, hormonal, or an environmental cause, generating pathways that often altogether play a synergistic role in the development of ASD pathogenesis. Furthermore, the metabolic origin of ASD should be important as well. A balanced diet consisting of the essential and special nutrients, alongside the recommended caloric intake, is highly recommended to promote growth and development that withstand the physiologic and behavioral challenges experienced by ASD children. In this review paper, we evaluated many studies that show a relationship between ASD and diet to develop a better understanding of the specific effects of the overall diet and the individual nutrients required for this population. This review will add a comprehensive update of knowledge in the field and shed light on the possible nutritional deficiencies, metabolic impairments (particularly in the gut microbiome), and malnutrition in individuals with ASD, which should be recognized in order to maintain the improved socio-behavioral habit and physical health.

Due to the three domains of the colchicine-site which is conducive to the combination with small molecule compounds, colchicine-site on the tubulin has become a common target for antitumor drug development, and accordingly, a large number of tubulin inhibitors binding to the colchicine-site have been reported and evaluated over the past years. In this study, tubulin inhibitors targeting the colchicine-site and their application as antitumor agents were reviewed based on the literature from 2015 to 2019. Tubulin inhibitors were classified into ten categories according to the structural features, including colchicine derivatives, CA-4 analogs, chalcone analogs, coumarin analogs, indole hybrids, quinoline and quinazoline analogs, lignan and podophyllotoxin derivatives, phenothiazine analogs, N-heterocycle hybrids and others. Most of them displayed potent antitumor activity, including antiproliferative effects against Multi-Drug-Resistant (MDR) cell lines and antivascular properties, both in vitro and in vivo. In this review, the design, synthesis and the analysis of the structure-activity relationship of tubulin inhibitors targeting the colchicine-site were described in detail. In addition, multi-target inhibitors, anti-MDR compounds, and inhibitors bearing antitumor activity in vivo are further listed in tables to present a clear picture of potent tubulin inhibitors, which could be beneficial for medicinal chemistry researchers.

Photodynamic Therapy (PDT) is a promising alternative treatment for malignancies based on photochemical reaction induced by Photosensitizers (PS) under light irradiation. Recent studies show that PDT caused the abundant release of exosomes from tumor tissues. It is well-known that exosomes as carriers play an important role in cell-cell communication through transporting many kinds of bioactive molecules (e.g. lipids, proteins, mRNA, miRNA and lncRNA). Therefore, to explore the role of exosomes in photodynamic anticancer therapy has been attracting significant attention. In the present paper, we will briefly introduce the basic principle of PDT and exosomes, and focus on discussing the role of exosomes in photodynamic anticancer therapy, to further enrich and boost the development of PDT.

Objective: This study aimed to systematically investigate whether anti-androgens could significantly reduce Obsessive-Compulsive Disorder (OCD) symptoms compared to placebo or usual care in OCD patients. Methods: PubMed, EMBASE, CENTRAL and International Clinical Trials Registry Platform (ICTRP) databases were searched up to October 2018 using relevant keywords. All randomized and if not available non-randomized studies conducted on a population including OCD patients who were administered with anti-androgen, which reported changes in their symptoms, were included. The studies on compulsive hypersexuality were excluded. Required data were extracted from full-text of the included articles by two independent authors. One randomized and four non-randomized trials were found. Results: The only randomized trial showed that flutamide, an anti-androgen agent, was effective in reducing compulsion scores in male OCD patients with comorbid Tourette syndrome, compared to placebo. Three out of four non-randomized trials showed that different anti-androgens including finasteride, cyproterone acetate and triptorelin were effective in reducing OCD symptoms. The only study, which failed to show the efficacy of an anti-androgen agent, administered OCD patients with flutamide. Despite the positive results, available studies provide the evidence with low quality based on the Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) approach. Conclusion: Available studies are not sufficient for a precise answer to our study question. There is still a need for further large randomized blinded clinical trials to evaluate the effectiveness of antiandrogens in OCD patients. It is recommended that gender, comorbidities and subscales of Yale- Brown Obsessive-Compulsive Score (Y-BOCS) should be considered in designing the studies and interpreting their results.

The concentrations of metals in the environment are still not within the recommended limits as set by the regulatory authorities in various countries because of human activities. They can enter the food chain and bioaccumulate in soft and hard tissues/organs, often with a long half-life of the metal in the body. Metal exposure has a negative impact on bone health and may result in osteoporosis and increased fracture risk depending on concentration and duration of metal exposure and metal species. Bones are a long-term repository for lead and some other metals, and may approximately contain 90% of the total body burden in birds and mammals. The present review focuses on the most common metals found in contaminated areas (mercury, cadmium, lead, nickel, chromium, iron, and aluminum) and their effects on bone tissue, considering the possibility of the long-term bone accumulation, and also some differences that might exist between different age groups in the whole population.

In the last decade, the use of carbon nanotubes and graphenes has been on the rise for various nanobiotechnological applications. Owing to their special characteristics, these two nanostructures of carbon allotropes have been studied for their capacity in the detection and treatment of many diseases. On the other hand, curcumin, a well-known antioxidant and anticancer natural product, is being extensively studied for numerous medicinal applications. Interestingly, many reports have shown great potentials of conjugates of curcumin and carbon nanotubes or graphenes. These conjugates, when properly designed and functionalized with biomolecules, could represent the valuable properties of each component alone while they could be effective in overcoming the poor solubility issues of both curcumin and Carbon Nanomaterials (CNMs). In this case, curcumin conjugates with CNMs seem to be very promising in biosensing applications and the detection of many biomolecules, especially, curcumin has been reported to be very effective with these conjugates. Also, the delivery of curcumin using functionalized SWCNTs was evaluated for its ability to load and release curcumin, to protect curcumin from degradation and to enhance its solubility. It is proposed that other properties of these conjugates are still to be discovered and the interdisciplinary approaches among biology, medicine, chemistry, and material engineering will accelerate the applications of these novel materials. This review aims to summarize the findings on the applications of CNM conjugates of curcumin.

Background: Imidazo[2,1-b]thiazole, a well-known fused five-membered hetrocycle is one of the most promising and versatile moieties in the area of medicinal chemistry. Derivatives of imidazo[2,1-b]thiazole have been investigated for the development of new derivatives that exhibit diverse pharmacological activities. This fused heterocycle is also a part of a number of therapeutic agents. Objective: To review the extensive pharmacological activities of imidazo[2,1-b]thiazole derivatives and the new molecules developed between 2000-2018 and their usefulness. Method: Thorough literature review of all relevant papers and patents was conducted. Conclusion: The present review, covering a number of aspects, is expected to provide useful insights in the design of imidazo[2,1-b]thiazole-based compounds and would inspire the medicinal chemists for a comprehensive and target-oriented information to achieve a major breakthrough in the development of clinically viable candidates.