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Repurposing Antihypertensive Drugs for the Management of Alzheimer's Disease

Law CSW, Yeong KY

Curr Med Chem, 2021;28(9):1716-1730.
PMID: 32164502 DOI: 10.2174/0929867327666200312114223

Alzheimer's disease (AD) is a neurodegenerative disorder that has affected millions of people worldwide. However, currently, there is no treatment to cure the disease. The AD drugs available in the market only manage the disease symptomatically and the effects are usually short-term. Thus, there is a need to look at alternatives AD therapies. This literature review aims to shed some light on the potential of repurposing antihypertensives to treat AD. Mid-life hypertension has not only been recognised as a risk factor for AD, but its relation with AD has also been well established. Hence, antihypertensives were postulated to be beneficial in managing AD. Four classes of antihypertensives, as well as their potential limitations and prospects in being utilised as AD therapeutics, were discussed in this review.
Benzimidazoles in Drug Discovery: A Patent Review

Law CSW, Yeong KY

ChemMedChem, 2021 06 17;16(12):1861-1877.
PMID: 33646618 DOI: 10.1002/cmdc.202100004

Benzimidazole is a heterocyclic ring system that has been widely studied in the pharmaceutical field. For the past decade, numerous benzimidazole derivatives have been synthesized and evaluated for their wide range of pharmacological activities, which are beneficial for drug development. This article presents the biological effects of benzimidazole derivatives in each invention from 2015 to 2020. Two patent databases, Google Patents and Lens, were used to locate relevant granted patent applications. Specifically, this review delineates the role of patented benzimidazoles from a disease-centric perspective and examines the mechanisms of action of these compounds in related diseases. Most of the benzimidazoles have shown good activities against various target proteins. Whilst several of them have progressed into clinical trials, most patents presented novel therapeutic approaches for respective target diseases. Hence, their potential in being developed into clinical drugs are also discussed.
Current trends of benzothiazoles in drug discovery: a patent review (2015-2020)

Law CSW, Yeong KY

Expert Opin Ther Pat, 2022 Jan 17.
PMID: 34986720 DOI: 10.1080/13543776.2022.2026327

INTRODUCTION: Benzothiazole is a bicyclic ring system composed of thiazole and benzene rings. It is present as an important pharmacophore in many marketed drugs. The notable potential of benzothiazoles as therapeutic agent for different target diseases has prompted a growing interest in benzothiazole-based drug development in recent years.
AREAS COVERED: This review of 55 benzothiazole-related patents, filed from 2015 to 2020, covers a wide range of pharmacological activities. These patents were collated from Google Patents and Lens search engines. The inventions were categorized and discussed based on their respective group of target diseases, including metabolic diseases, cancer, inflammation, neurodegeneration, viral diseases, bacterial infections, fibrosis and thrombosis.
EXPERT OPINION: Benzothiazole has shown to be a scaffold with great pharmacological importance and thus, serves as a building block for the development of derivatives having high therapeutic activity. Benzothiazole derivatives were patented for a range of therapeutic applications, with a special focus on cancer research. Several compounds have the potential to progress into the market, given that they exert both selectivity and in vivo efficacy. Others require a more thorough study to obtain adequate information on the compounds.
Fulltext The Role of Interferon-α in Neurodegenerative Diseases: A Systematic Review

Hui BSM, Zhi LR, Retinasamy T, Arulsamy A, Law CSW, Shaikh MF, et al.

J Alzheimers Dis, 2023;94(s1):S45-S66.
PMID: 36776068 DOI: 10.3233/JAD-221081

BACKGROUND: Neurodegenerative diseases (NDs) impose significant financial and healthcare burden on populations all over the world. The prevalence and incidence of NDs have been observed to increase dramatically with age. Hence, the number of reported cases is projected to increase in the future, as life spans continues to rise. Despite this, there is limited effective treatment against most NDs. Interferons (IFNs), a family of cytokines, have been suggested as a promising therapeutic target for NDs, particularly IFN-α, which governs various pathological pathways in different NDs.
OBJECTIVE: This systematic review aimed to critically appraise the currently available literature on the pathological role of IFN-α in neurodegeneration/NDs.
METHODS: Three databases, Scopus, PubMed, and Ovid Medline, were utilized for the literature search.
RESULTS: A total of 77 journal articles were selected for critical evaluation, based on the inclusion and exclusion criteria. The studies selected and elucidated in this current systematic review have showed that IFN-α may play a deleterious role in neurodegenerative diseases through its strong association with the inflammatory processes resulting in mainly neurocognitive impairments. IFN-α may be displaying its neurotoxic function via various mechanisms such as abnormal calcium mineralization, activation of STAT1-dependent mechanisms, and increased quinolinic acid production.
CONCLUSION: The exact role IFN-α in these neurodegenerative diseases have yet to be determine due to a lack in more recent evidence, thereby creating a variability in the role of IFN-α. Future investigations should thus be conducted, so that the role played by IFN-α in neurodegenerative diseases could be delineated.