Search

Amrita Muralikrishnan,1 Mahendran Sekar,1 Vinoth Kumarasamy,2 Siew Hua Gan,1 Subban Ravi,3 Vetriselvan Subramaniyan,4 Ling Shing Wong,5 Yuan Seng Wu,6 Farrah Syazana Khattulanuar,7 Nur Najihah Izzati Mat Rani7 1School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, Malaysia; 2Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia; 3Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 4Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor 47500, Malaysia; 5Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, Malaysia; 6Sunway Microbiome Centre & Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 7Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, MalaysiaCorrespondence: Mahendran Sekar, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, Malaysia, Email mahendran.sekar@moansh.edu Vinoth Kumarasamy, Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, 56000, Malaysia, Email vinoth@ukm.edu.myAbstract: Decursin is a pyranocoumarin compounds which are rare secondary metabolic plant products, isolated from the roots of Angelica gigas (A. gigas). The native Korean species Angelica gigas Nakai (AGN) is widely used as a remedy for a variety of medical conditions including hematopoiesis, improving women’s circulation, as sedatives, analgesics and tonic. It is unique because of the presence of substantial amounts of pyranocoumarins including decursin, decursinol, and decursinol angelate. In this review, we provide a comprehensive insight into the distribution, morphology, and chemical composition of A. gigas. A detailed discussion regarding the biological applications of decursin based on the literature retrieved from PubMed, ScienceDirect, Scopus, and Google Scholar from 2000 to the present has been discussed. Both in vitro and in vivo studies have demonstrated that decursin has potential neuroprotective, anti-inflammatory, anti-melanogenic, anti-angiogenic, antioxidant, and anti-visceral properties. Mechanistic findings establish its significance in regulating important signalling pathways, triggering apoptosis, and preventing metastasis in different cancer types. The review additionally addressed the isolation methods, biosynthesis, physiochemical characteristics, toxicity and pharmacokinetic profile of decursin. The present state of clinical studies including A. gigas is investigated, emphasizing its advancements and possibilities in the field of translational medicine. Keywords: decursin, Angelica gigas, pyranocoumarins, biosynthesis, pharmacology

Aathira Sujathan Nair,1 Mahendran Sekar,1 Siew Hua Gan,1 Vinoth Kumarasamy,2 Vetriselvan Subramaniyan,3 Yuan Seng Wu,4 Nur Najihah Izzati Mat Rani,5 Subban Ravi,6 Ling Shing Wong7 1School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia; 2Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia; 3Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 4Sunway Microbiome Centre & Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 5Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, Malaysia; 6Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 7Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, MalaysiaCorrespondence: Mahendran Sekar, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia, Email mahendran.sekar@monash.edu Vinoth Kumarasamy, Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, 56000, Malaysia, Email vinoth@ukm.edu.myAbstract: Lawsone, a naturally occurring organic compound also called hennotannic acid, obtained mainly from Lawsonia inermis (Henna). It is a potential drug-like molecule with unique chemical and biological characteristics. Traditionally, henna is used in hair and skin coloring and is also a medicinal herb for various diseases. It is also widely used as a starting material for the synthesis of various drug molecules. In this review, we investigate on the chemistry, biosynthesis, physical and biological properties of lawsone. The results showed that lawsone has potential antioxidant, anti-inflammatory, antimicrobial and antitumor properties. It also induces cell cycle inhibition and programmed cell death in cancer, making it a potential chemotherapeutic agent. Additionally, inhibition of pro-inflammatory cytokine production makes it an essential treatment for inflammatory diseases. Exploration of its biosynthetic pathway can pave the way for its development into targets for new drug development. In future, well-thought-out clinical studies should be made to verify its safety and efficacy. Keywords: lawsone, Lawsonia inermis, henna, antitumor, antioxidant, anti-inflammatory, antimicrobial

Muhamad Azrul Amir Yusri,1 Mahendran Sekar,2,3 Ling Shing Wong,4 Siew Hua Gan,2 Subban Ravi,5 Vetriselvan Subramaniyan,6 Nur Najihah Izzati Mat Rani,7 Kumarappan Chidambaram,8 M Yasmin Begum,9 Mohankumar Ramar,10 Sher Zaman Safi,11 Siddharthan Selvaraj,12 Yuan Seng Wu,13 Palanisamy Revathy,14 Shivkanya Fuloria,15 Neeraj Kumar Fuloria,15 Pei Teng Lum,1 Sinouvassane Djearamane16 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, Malaysia; 2School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, Malaysia; 3Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, India; 4Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia; 5Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 6Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, Malaysia; 7Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, Malaysia; 8Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia; 9Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia; 10Department of Surgical Research, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, RI, USA; 11Faculty of Medicine, Bioscience and Nursing, MAHSA University, Bandar Saujana Putra, Jenjarom, Selangor, Malaysia; 12Faculty of Dentistry, AIMST University, Bedong, Kedah, Malaysia; 13Department of Biological Sciences and Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Subang Jaya, Selangor, Malaysia; 14Department of Computer Applications, Gobi Arts & Science College, Gobichettipalayam, Tamil Nadu, India; 15Faculty of Pharmacy, AIMST University, Bedong, Kedah, Malaysia; 16Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Perak, MalaysiaCorrespondence: Ling Shing Wong, Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia, Tel +6014 3034057, Email lingshing.wong@newinti.edu.my Sinouvassane Djearamane, Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Perak, Malaysia, Tel +6016 4037685, Email biochsinouvas07@gmail.comAbstract: Celastrol is a naturally occurring chemical isolated from Tripterygium wilfordii Hook. f., root extracts widely known for their neuroprotective properties. In this review, we focus on the efficacy of celastrol in mitigating memory impairment (MI) in both in vivo and in vitro models. Scopus, PubMed and Web of Science databases were utilised to locate pertinent literatures that explore the effects of celastrol in the brain, including its pharmacokinetics, bioavailability, behavioral effects and some of the putative mechanisms of action on memory in many MI models. To date, preclinical studies strongly suggest that celastrol is highly effective in enhancing the cognitive performance of MI animal models, particularly in the memory domain, including spatial, recognition, retention and reference memories, via reduction in oxidative stress and attenuation of neuro-inflammation, among others. This review also emphasised the challenges and potential associated enhancement of medication delivery for MI treatment. Additionally, the potential structural alterations and derivatives of celastrol in enhancing its physicochemical and drug-likeness qualities are examined. The current review demonstrated that celastrol can improve cognitive performance and mitigate MI in several preclinical investigations, highlighting its potential as a natural lead molecule for the design and development of a novel neuroprotective medication.Graphical Abstract: Keywords: celastrol, memory impairment, neuroprotection, drug discovery, natural products

Naurah Nabihah Nasir,1 Mahendran Sekar,2,3 Subban Ravi,4 Ling Shing Wong,5 Sreenivas Patro Sisinthy,6 Siew Hua Gan,2 Vetriselvan Subramaniyan,7 Kumarappan Chidambaram,8 Nur Najihah Izzati Mat Rani,6 M Yasmin Begum,9 Mohankumar Ramar,10 Sher Zaman Safi,11 Siddharthan Selvaraj,12 Senthil Kumar Chinna Maruthu,13 Shivkanya Fuloria,14 Neeraj Kumar Fuloria,14 Pei Teng Lum,1 Sinouvassane Djearamane15 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, Malaysia; 2School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, 47500, Malaysia; 3Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospital, Saveetha University, Chennai, Tamil Nadu, 600077, India; 4Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, 641021, India; 5Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, Malaysia; 6Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, Malaysia; 7Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, Malaysia; 8Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia; 9Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, 61421, Saudi Arabia; 10Department of Surgical Research, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, RI, 02903, USA; 11Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jenjarom, Selangor, 42610, Malaysia; 12Faculty of Dentistry, AIMST University, Bedong, Kedah, 08100, Malaysia; 13Department of Pharmacology, Karpagam College of Pharmacy, Coimbatore, Tamilnadu, 641032, India; 14Faculty of Pharmacy, AIMST University, Bedong, Kedah, 08100, Malaysia; 15Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Perak, 31900, MalaysiaCorrespondence: Ling Shing Wong, Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, Malaysia, Tel +6014 – 3034057, Email lingshing.wong@newinti.edu.my Sinouvassane Djearamane, Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, 31900, Perak, Malaysia, Tel +6016 – 4037685, Email biochsinouvas07@gmail.comAbstract: Streptonigrin is an aminoquinone alkaloid isolated from Streptomyces flocculus and is gaining attention as a drug molecule owing to its potential antitumor and antibiotic effects. It was previously used as an anticancer drug but has been discontinued because of its toxic effects. However, according to the most recent studies, the toxicity of streptonigrin and its structurally modified derivatives has been reduced while maintaining their potential pharmacological action at lower concentrations. To date, many investigations have been conducted on this molecule and its derivatives to determine the most effective molecule with low toxicity to enable new drug discovery. Therefore, the main objective of this study is to provide a comprehensive review and to discuss the prospects for streptonigrin and its derived compounds, which may boost the molecule as a highly interesting target molecule for new drug design, development and therapy. To complete this review, relevant literature was collected from several scientific databases, including Google Scholar, PubMed, Scopus and ScienceDirect. Following a complete screening, the obtained information is summarized in the present review to provide a good reference and accelerate the development and utilization of streptonigrin and its derivatives as pharmaceuticals.Graphical Abstract: Keywords: streptonigrin, chemistry, biosynthesis, pharmacology, anticancer, antibacterial

Siddharthan Selvaraj,1,2 Nyi Nyi Naing,1 Nadiah Wan-Arfah,3 Sinouvassane Djearamane,4 Ling Shing Wong,5 Vetriselvan Subramaniyan,6 Neeraj Kumar Fuloria,7 Mahendran Sekar,8 Shivkanya Fuloria,7 Mauro Henrique Nogueira Guimarães de Abreu9 1Faculty of Medicine, Medical Campus, Universiti Sultan Zainal Abidin, Kuala Terengganu, Terengganu, 20400, Malaysia; 2Faculty of Dentistry, AIMST University, Bedong, Kedah, 08100, Malaysia; 3Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Kuala Terengganu, Terengganu, 20400, Malaysia; 4Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Perak, 31900, Malaysia; 5Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, Malaysia; 6Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jen jarom, Selangor, 42610, Malaysia; 7Faculty of Pharmacy, AIMST University, Bedong, Kedah, 08100, Malaysia; 8Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, Malaysia; 9School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, CEP 31270- 901, BrazilCorrespondence: Nyi Nyi Naing; Sinouvassane Djearamane, Email syedhatim@unisza.edu.my; sinouvassane@utar.edu.myIntroduction: Oral conditions exist worldwide, and are related with astounding morbidity. Indian adults’ incidence of mild and moderate periodontal conditions was nearly 25%, while about 19% of adults experience severe periodontitis.Objective: The aim of this study was to analyse epidemiological factors of periodontal disease among a south Indian population based on the role of sociodemographic factors, habitual factors and set of oral health knowledge, attitude, and behaviour measures.Methods: A sample of 288 participants above 18 years of age residing in Tamil Nadu, India took part in this cross-sectional study. Based on WHO criteria, periodontal disease was measured in our study. Age, ethnicity, smoking, education, and oral health behavior were found to be the covariates. Ordinal logistic regression analysis using R version 3.6.1 was utilized to study the various factors that influence periodontal disease among south Indian adults.Results: Various demographic factors such as age between 25 and 34 years (AOR = 2.25; 95% CI 1.14– 4.55), 35– 44 years (AOR = 1.80; 95% CI 0.89– 3.64), ≥ 45 years old (AOR = 2.89; 95% CI 1.41– 6.01), ethnicity (AOR = 2.71; 95% CI 1.25– 5.81), smoking (AOR = 0.38; 95% CI 0.16– 0.65), primary level education (AOR = 0.07; 95% CI 0.01– 0.50) high school level education (AOR = 0.06; 95% CI 0.01– 0.27), university level education (AOR = 0.08; 95% CI 0.01– 0.36) and an individual’s oral health behavior (AOR = 0.59; 95% CI 0.32– 1.08) were found to be related with periodontal disease among the south Indian population. The maximum log likelihood residual deviance value was 645.94 in the final model.Conclusion: Based on our epidemiological findings, sociodemographic, habitual factors and oral health behavior play a vital role in an individual’s periodontal status among south Indian adults. An epidemiological model derived from the factors from our study will help to bring better understanding of the disease and to implement various preventive strategies to eliminate the causative factors.Keywords: periodontal disease, epidemiology, modelling, socio-demography, habits

Nurul Amirah Mohd Zaid,1,* Mahendran Sekar,1,* Srinivasa Reddy Bonam,2,* Siew Hua Gan,3 Pei Teng Lum,1 M Yasmin Begum,4 Nur Najihah Izzati Mat Rani,5 Jaishree Vaijanathappa,6 Yuan Seng Wu,7,8 Vetriselvan Subramaniyan,9 Neeraj Kumar Fuloria,10 Shivkanya Fuloria10 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, 30450, Malaysia; 2Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université de Paris, Paris, France; 3School of Pharmacy, Monash University Malaysia, Selangor Darul Ehsan, 47500, Malaysia; 4Department of Pharmaceutics, College of Pharmacy, King Khalid University (KKU), Asir-Abha, 61421, Saudi Arabia; 5Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, 30450, Malaysia; 6Faculty of Life Sciences, JSS Academy of Higher Education and Research Mauritius, Vacoas-Phoenix, Mauritius; 7Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 8Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 9Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, 42610, Malaysia; 10Faculty of Pharmacy, AIMST University, Kedah, 08100, Malaysia*These authors contributed equally to this workCorrespondence: Mahendran SekarDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, 30450, Perak, MalaysiaTel +6016 – 3346653Fax +605 – 2536634Email mahendransekar@unikl.edu.myAbstract: The skin is the largest organ in the human body, composed of the epidermis and the dermis. It provides protection and acts as a barrier against external menaces like allergens, chemicals, systemic toxicity, and infectious organisms. Skin disorders like cancer, dermatitis, psoriasis, wounds, skin aging, acne, and skin infection occur frequently and can impact human life. According to a growing body of evidence, several studies have reported that natural products have the potential for treating skin disorders. Building on this information, this review provides brief information about the action of the most important in vitro and in vivo research on the use of ten selected natural products in inflammatory, neoplastic, and infectious skin disorders and their mechanisms that have been reported to date. The related studies and articles were searched from several databases, including PubMed, Google, Google Scholar, and ScienceDirect. Ten natural products that have been reported widely on skin disorders were reviewed in this study, with most showing anti-inflammatory, antioxidant, anti-microbial, and anti-cancer effects as the main therapeutic actions. Overall, most of the natural products reported in this review can reduce and suppress inflammatory markers, like tumor necrosis factor-alpha (TNF-α), scavenge reactive oxygen species (ROS), induce cancer cell death through apoptosis, and prevent bacteria, fungal, and virus infections indicating their potentials. This review also highlighted the challenges and opportunities of natural products in transdermal/topical delivery systems and their safety considerations for skin disorders. Our findings indicated that natural products might be a low-cost, well-tolerated, and safe treatment for skin diseases. However, a larger number of clinical trials are required to validate these findings. Natural products in combination with modern drugs, as well as the development of novel delivery mechanisms, represent a very promising area for future drug discovery of these natural leads against skin disorders.Keywords: natural products, skin disorder, dermatitis, psoriasis, skin cancer, anti-inflammatory, drug delivery

Shazalyana Azman,1,2 Mahendran Sekar,1 Suzana Wahidin,2 Siew Hua Gan,3 Jaishree Vaijanathappa,4 Srinivasa Reddy Bonam,5 Mallika Alvala,6 Pei Teng Lum,1 Vandana Thakur,7 Jayesh V Beladiya,7 Anita A Mehta7 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 2Bioengineering and Technology Section, Universiti Kuala Lumpur Malaysian Institute of Chemical & Bioengineering Technology, Alor Gajah, Melaka, 78000, Malaysia; 3School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, 47500, Malaysia; 4Faculty of Life Sciences, JSS Academy of Higher Education and Research Mauritius, Republic of Mauritius; 5Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université De Paris, Paris, F-75006, France; 6MARS Training Academy, Hyderabad, 500037, India; 7Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, Gujarat, IndiaCorrespondence: Mahendran SekarDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, No. 3 Jalan Greentown, Ipoh, Perak, 30450, MalaysiaTel +6016 – 3346653Fax +605 – 2536634Email mahendransekar@unikl.edu.myBackground: Asthma is a chronic lung disease, which causes wheezing, tightness in the chest, shortness of breath and coughing. In the wake of coronavirus disease 2019 (COVID-19), which affect the lungs, asthma patients are at high risk. Embelin, a natural benzoquinone obtained mainly from Embelia ribes Burm, has excellent biological properties, including protection against acute asthma. However, since asthma is a chronic and multi-factorial inflammatory disease, asthma conferred by a single allergen in an animal may not be clinically significant. Therefore, the purpose of the current study was to evaluate the effectiveness of embelin against ovalbumin (OVA)-lipopolysaccharide (LPS)-induced severe airway inflammation in experimental animals and to investigate the plausible mechanism of action.Methods: Rats (n=36) were divided into six groups. Group I served as a normal control. Groups II–VI were sensitised with severe allergens (OVA and LPS) on day 7, 14 and 21, followed by OVA and LPS challenge for 30 min three times/week for 3 weeks. Group II acted as an asthmatic disease control and received only vehicle. On the other hand, groups III–V received embelin (12.5, 25 and 50 mg/kg, P.O. respectively) while group VI received a standard dexamethasone (2.5 mg/kg, P.O.) for 15 days from day 27. Lung function parameters, including the respiratory rate, tidal volume and airflow rate were measured at the end of the experiment (day 42). The total and differential counts of leukocytes in the blood and bronchoalveolar fluid (BALF) were calculated. Th2-mediated serum pro-inflammatory cytokines such as interleukin (IL)-4, IL-5 and IL-13 levels were analyzed. At the end of the study protocol, the lung tissues were removed for a histopathology study. Additionally, a molecular docking simulation on embelin and standard dexamethasone was applied to support the in vivo findings.Results: Significant inhibition of eosinophils, neutrophils, lymphocytes and monocytes in the blood and the BALF was seen in the groups, which received embelin (25 and 50 mg/kg) and dexamethasone (2.5 mg/kg). Moreover, the lung function parameters were normalised by embelin (25 and 50 mg/kg) treatment significantly. The lung histopathological changes confirmed the protective effect of embelin against severe airway inflammation. The docking findings indicated good binding efficacy of embelin to IL-13.Conclusion: Overall, our findings indicate that embelin can alleviate severe airway inflammation in OVA-LPS-induced model of allergic asthma occurring by suppression of Th2-mediated immune response. Due to its promising anti-asthmatic effect, it is recommended that embelin should be investigated in clinical trials against asthma. It should also be further explored against COVID-19 or COVID-like diseases due to its ameliorative effects on cytokines and immune cell infiltration.Keywords: embelin, OVA-LPS-induced severe asthma, allergic inflammation, Th2-mediated inflammatory cells, IL-13 molecular docking, COVID-19

Kah Min Yap,1 Mahendran Sekar,1 Shivkanya Fuloria,2 Yuan Seng Wu,3,4 Siew Hua Gan,5 Nur Najihah Izzati Mat Rani,6 Vetriselvan Subramaniyan,7 Chandrakant Kokare,8 Pei Teng Lum,1 M Yasmin Begum,9 Shankar Mani,10 Dhanalekshmi Unnikrishnan Meenakshi,11 Kathiresan V Sathasivam,12 Neeraj Kumar Fuloria2 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 2Faculty of Pharmacy, AIMST University, Kedah, 08100, Malaysia; 3Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 4Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 5School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, 47500, Malaysia; 6Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 7Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, 42610, Malaysia; 8Department of Pharmaceutics, Sinhgad Technical Education Society’s, Sinhgad Institute of Pharmacy, Narhe, Pune, 411041, India; 9Department of Pharmaceutics, College of Pharmacy, King Khalid University (KKU), Asir-Abha, 61421, Saudi Arabia; 10Department of Pharmaceutical Chemistry, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Mandya, Karnataka, 571418, India; 11College of Pharmacy, National University of Science and Technology, Muscat, 130, Oman; 12Faculty of Applied Sciences, AIMST University, Kedah, 08100, MalaysiaCorrespondence: Neeraj Kumar Fuloria; Shivkanya FuloriaFaculty of Pharmacy, AIMST University, Kedah, 08100, MalaysiaTel +60 16 4037685; +60 14 3034057Email neerajkumar@aimst.edu.my; shivkanya_fuloria@aimst.edu.myAbstract: Despite recent advances in the diagnosis and treatment of breast cancer (BC), it remains a global health issue affecting millions of women annually. Poor prognosis in BC patients is often linked to drug resistance as well as the lack of effective therapeutic options for metastatic and triple-negative BC. In response to these unmet needs, extensive research efforts have been devoted to exploring the anti-BC potentials of natural products owing to their multi-target mechanisms of action and good safety profiles. Various medicinal plant extracts/essential oils and natural bioactive compounds have demonstrated anti-cancer activities in preclinical BC models. Despite the promising preclinical results, however, the clinical translation of natural products has often been hindered by their poor stability, aqueous solubility and bioavailability. There have been attempts to overcome these limitations, particularly via the use of nano-based drug delivery systems (NDDSs). This review highlights the tumour targeting mechanisms of NDDSs, the advantages and disadvantages of the major classes of NDDSs and their current clinical status in BC treatment. Besides, it also discusses the proposed anti-BC mechanisms and nanoformulations of nine medicinal plants’ extracts/essential oils and nine natural bioactive compounds; selected via the screening of various scientific databases, including PubMed, Scopus and Google Scholar, based on the following keywords: “Natural Product AND Nanoparticle AND Breast Cancer”. Overall, these nanoformulations exhibit improved anti-cancer efficacy against preclinical BC models, with some demonstrating biocompatibility with normal cell lines and mouse models. Further clinical studies are, however, warranted to ascertain their efficacy and biocompatibility in humans.Keywords: breast cancer, drug delivery, molecular mechanisms, nanoparticles, natural products, phytomedicine

Mohd Nasarudin Watroly,1 Mahendran Sekar,1 Shivkanya Fuloria,2 Siew Hua Gan,3 Srikanth Jeyabalan,4 Yuan Seng Wu,5,6 Vetriselvan Subramaniyan,7 Kathiresan V Sathasivam,8 Subban Ravi,9 Nur Najihah Izzati Mat Rani,10 Pei Teng Lum,1 Jaishree Vaijanathappa,11 Dhanalekshmi Unnikrishnan Meenakshi,12 Shankar Mani,13 Neeraj Kumar Fuloria2 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 2Faculty of Pharmacy & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, Malaysia; 3School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, 47500, Malaysia; 4Department of Pharmacology, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research (DU), Chennai, Tamil Nadu, 600116, India; 5Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 6Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 7Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, 42610, Malaysia; 8Faculty of Applied Science & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, Malaysia; 9Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, 640 021, India; 10Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 11Department of Pharmaceutical Chemistry, School of Life Sciences, JSS Academy of Higher Education and Research Mauritius, Vacoas, Mauritius; 12College of Pharmacy, National University of Science and Technology, Muscat, 130, Oman; 13Department of Pharmaceutical Chemistry, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Mandya, Karnataka, 571418, IndiaCorrespondence: Neeraj Kumar Fuloria; Shivkanya FuloriaFaculty of Pharmacy & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, MalaysiaTel +60 16 4037685; +60 14 3034057Email neerajkumar@aimst.edu.my; shivkanya_fuloria@aimst.edu.myAbstract: Anthraquinones (AQs) are found in a variety of consumer products, including foods, nutritional supplements, drugs, and traditional medicines, and have a wide range of pharmacological actions. Rubiadin, a 1,3-dihydroxy-2-methyl anthraquinone, primarily originates from Rubia cordifolia Linn (Rubiaceae). It was first discovered in 1981 and has been reported for many biological activities. However, no review has been reported so far to create awareness about this molecule and its role in future drug discovery. Therefore, the present review aimed to provide comprehensive evidence of Rubiadin’s phytochemistry, biosynthesis, physicochemical properties, biological properties and therapeutic potential. Relevant literature was gathered from numerous scientific databases including PubMed, ScienceDirect, Scopus and Google Scholar between 1981 and up-to-date. The distribution of Rubiadin in numerous medicinal plants, as well as its method of isolation, synthesis, characterisation, physiochemical properties and possible biosynthesis pathways, was extensively covered in this review. Following a rigorous screening and tabulating, a thorough description of Rubiadin’s biological properties was gathered, which were based on scientific evidences. Rubiadin fits all five of Lipinski’s rule for drug-likeness properties. Then, the in depth physiochemical characteristics of Rubiadin were investigated. The simple technique for Rubiadin’s isolation from R. cordifolia and the procedure of synthesis was described. Rubiadin is also biosynthesized via the polyketide and chorismate/o-succinylbenzoic acid pathways. Rubiadin is a powerful molecule with anticancer, antiosteoporotic, hepatoprotective, neuroprotective, anti-inflammatory, antidiabetic, antioxidant, antibacterial, antimalarial, antifungal, and antiviral properties. The mechanism of action for the majority of the pharmacological actions reported, however, is unknown. In addition to this review, an in silico molecular docking study was performed against proteins with PDB IDs: 3AOX, 6OLX, 6OSP, and 6SDC to support the anticancer properties of Rubiadin. The toxicity profile, pharmacokinetics and possible structural modifications were also described. Rubiadin was also proven to have the highest binding affinity to the targeted proteins in an in silico study; thus, we believe it may be a potential anticancer molecule. In order to present Rubiadin as a novel candidate for future therapeutic development, advanced studies on preclinical, clinical trials, bioavailability, permeability and administration of safe doses are necessary.Keywords: Rubiadin, Rubia cordifolia, biosynthesis, physicochemical properties, anticancer, pharmacology

Nur Zulaikha Azwa Zuraini,1 Mahendran Sekar,1 Yuan Seng Wu,2,3 Siew Hua Gan,4 Srinivasa Reddy Bonam,5 Nur Najihah Izzati Mat Rani,6 M Yasmin Begum,7 Pei Teng Lum,1 Vetriselvan Subramaniyan,8 Neeraj Kumar Fuloria,9 Shivkanya Fuloria9 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 2Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 3Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 4School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, 47500, Malaysia; 5Institut National de la Santé et de la Recherche Médicale, Centre de Recherché des Cordeliers, Sorbonne Université, Université de Paris, Paris, France; 6Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 7Department of Pharmaceutics, College of Pharmacy, King Khalid University (KKU), Asir-Abha, 61421, Saudi Arabia; 8Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, 42610, Malaysia; 9Faculty of Pharmacy & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, MalaysiaCorrespondence: Mahendran SekarDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, MalaysiaTel +6016 – 3346653Fax +605 – 2536634Email mahendransekar@unikl.edu.myAbstract: Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality in both developed and developing countries, affecting millions of individuals each year. Despite the fact that successful therapeutic drugs for the management and treatment of CVDs are available on the market, nutritional fruits appear to offer the greatest benefits to the heart and have been proved to alleviate CVDs. Experimental studies have also demonstrated that nutritional fruits have potential protective effects against CVDs. The aim of the review was to provide a comprehensive summary of scientific evidence on the effect of 10 of the most commonly available nutritional fruits reported against CVDs and describe the associated mechanisms of action. Relevant literatures were searched and collected from several scientific databases including PubMed, ScienceDirect, Google Scholar and Scopus. In the context of CVDs, 10 commonly consumed nutritious fruits including apple, avocado, grapes, mango, orange, kiwi, pomegranate, papaya, pineapple, and watermelon were analysed and addressed. The cardioprotective mechanisms of the 10 nutritional fruits were also compiled and highlighted. Overall, the present review found that the nutritious fruits and their constituents have significant benefits for the management and treatment of CVDs such as myocardial infarction, hypertension, peripheral artery disease, coronary artery disease, cardiomyopathies, dyslipidemias, ischemic stroke, aortic aneurysm, atherosclerosis, cardiac hypertrophy and heart failure, diabetic cardiovascular complications, drug-induced cardiotoxicity and cardiomyopathy. Among the 10 nutritional fruits, pomegranate and grapes have been well explored, and the mechanisms of action are well documented against CVDs. All of the nutritional fruits mentioned are edible and readily accessible on the market. Consuming these fruits, which may contain varying amounts of active constituents depending on the food source and season, the development of nutritious fruits-based health supplements would be more realistic for consistent CVD protection.Keywords: nutritional fruits, cardiovascular diseases, heart disease, antioxidant, hypertension, nutraceuticals

Kah Min Yap,1 Mahendran Sekar,1 Lay Jing Seow,1 Siew Hua Gan,2 Srinivasa Reddy Bonam,3 Nur Najihah Izzati Mat Rani,4 Pei Teng Lum,1 Vetriselvan Subramaniyan,5 Yuan Seng Wu,5 Neeraj Kumar Fuloria,6 Shivkanya Fuloria6 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, 30450, Perak, Malaysia; 2School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia; 3Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université de Paris, Paris, France; 4Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, 30450, Perak, Malaysia; 5Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, 42610, Malaysia; 6Faculty of Pharmacy, AIMST University, Kedah, 08100, MalaysiaCorrespondence: Mahendran Sekar Tel +6016 – 3346653Fax +605 – 2536634Email mahendransekar@unikl.edu.myAbstract: Globally, breast cancer is the most common cancer type and is one of the most significant causes of deaths in women. To date, multiple clinical interventions have been applied, including surgical resection, radiotherapy, endocrine therapy, targeted therapy and chemotherapy. However, 1) the lack of therapeutic options for metastatic breast cancer, 2) resistance to drug therapy and 3) the lack of more selective therapy for triple-negative breast cancer are some of the major challenges in tackling breast cancer. Given the safe nature of natural products, numerous studies have focused on their anti-cancer potentials. Mangifera indica, commonly known as mango, represents one of the most extensively investigated natural sources. In this review, we provide a comprehensive overview of M. indica extracts (bark, kernel, leaves, peel and pulp) and phytochemicals (mangiferin, norathyriol, gallotannins, gallic acid, pyrogallol, methyl gallate and quercetin) reported for in vitro and in vivo anti-breast cancer activities and their underlying mechanisms based on relevant literature from several scientific databases, including PubMed, Scopus and Google Scholar till date. Overall, the in vitro findings suggest that M. indica extracts and/or phytochemicals inhibit breast cancer cell growth, proliferation, migration and invasion as well as trigger apoptosis and cell cycle arrest. In vivo results demonstrated that there was a reduction in breast tumor xenograft growth. Several potential mechanisms underlying the anti-breast cancer activities have been reported, which include modulation of oxidative status, receptors, signalling pathways, miRNA expression, enzymes and cell cycle regulators. To further explore this medicinal plant against breast cancer, future research directions are addressed. The outcomes of the review revealed that M. indica extracts and their phytochemicals may have potential benefits in the management of breast cancer in women. However, to validate its utility in the creation of innovative and potent therapeutic agents to treat breast cancer, more dedicated research, especially clinical studies are needed to explore the anti-breast cancer potentials of M. indica extracts and their phytochemicals.Keywords: mango, Mangifera indica, mangiferin, breast cancer, molecular mechanism, natural products, women’s health

Shazalyana Azman,1,2,* Mahendran Sekar,1,* Srinivasa Reddy Bonam,3,* Siew Hua Gan,4 Suzana Wahidin,2 Pei Teng Lum,1 Shivsharan B Dhadde5 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 2Bioengineering and Technology Section, Universiti Kuala Lumpur Malaysian Institute of Chemical & Bioengineering Technology, Alor Gajah, Melaka, 78000, Malaysia; 3Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université De Paris, Paris, France; 4School of Pharmacy, Monash University Malaysia, Bandar Sunway Selangor Darul Ehsan, 47500, Malaysia; 5D.S.T.S. Mandal’s College of Pharmacy, Solapur, India*These authors contributed equally to this workCorrespondence: Mahendran SekarDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, No. 3 Jalan Greentown, Ipoh, Perak, 30450, MalaysiaTel +60163346653Fax +6052536634Email mahendransekar@unikl.edu.myAbstract: Asthma is a chronic inflammatory disease of the respiratory tract in which the numerous immune cells, including eosinophils, neutrophils, macrophages, T-lymphocytes, mast cells and epithelial lining play key roles. The numerous anti-asthmatic drugs are available in modern medicine to treat asthma, but they have several disadvantages, including side effects and the cost variations, which compromise treatment compliance. The literature review reveals that traditional herbal medicines have good potential as alternative treatment and management for asthma. However, communities hesitated to use the traditional herbal medicines due to lack of established mechanism of action about their anti-asthmatic potential. The present review aimed to summarise the information stated in the literature about the potential effect of traditional medicinal plants (TMPs) conferring protection against ovalbumin (OVA)-induced asthma model. The literature search was conducted in database like PubMed, Scopus, Google Scholar and ScienceDirect. After screening through the literature from 2011 to date, a total of 27 medicinal plants and two polyherbal extracts have been reported to be used as traditional herbal medicines and also utilised to be tested against OVA-induced asthma, were included. We found them to be an important alternative source of treatment for asthma, since some have comparable efficacies with drugs commonly used in the modern system against asthma. All the reported medicinal plants confirmed their traditional use against asthma or its related inflammation. The present review provides faith in traditional information and also offers new insight into the potential of natural products against asthma.Keywords: OVA-induced asthma, traditional medicinal plants, natural products, allergic asthma, inflammation, T-helper cells

Nur Sakinah Muhamad Fadzil,1 Mahendran Sekar,1 Siew Hua Gan,2 Srinivasa Reddy Bonam,3 Yuan Seng Wu,4 Jaishree Vaijanathappa,5 Subban Ravi,6 Pei Teng Lum,1 Shivsharan B Dhadde7 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, Malaysia; 2School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia; 3Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université de Paris, Paris, France; 4Department of Biochemistry, School of Medicine, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Bandar Saujana Putra, Selangor, Malaysia; 5Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Mysuru, Karnataka, India; 6Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 7D.S.T.S. Mandal’s College of Pharmacy, Solapur, Maharashtra, IndiaCorrespondence: Mahendran SekarDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, No. 3 Jalan Greentown, Ipoh, 30450, Perak, MalaysiaTel +6016 – 3346653Fax +605 – 2536634Email mahendransekar@unikl.edu.myAbstract: Swertiamarin, a seco-iridoid glycoside, is mainly found in Enicostemma littorale Blume (E. littorale) and exhibits therapeutic activities for various diseases. The present study aimed to provide a review of swertiamarin in terms of its phytochemistry, physicochemical properties, biosynthesis, pharmacology and therapeutic potential. Relevant literature was collected from several scientific databases, including PubMed, ScienceDirect, Scopus and Google Scholar, between 1990 and the present. This review included the distribution of swertiamarin in medicinal plants and its isolation, characterization, physicochemical properties and possible biosynthetic pathways. A comprehensive summary of the pharmacological activities, therapeutic potential and metabolic pathways of swertiamarin was also included after careful screening and tabulation. Based on the reported evidence, swertiamarin meets all five of Lipinski’s rules for drug-like properties. Thereafter, the physicochemical properties of swertiamarin were detailed and analyzed. A simple and rapid method for isolating swertiamarin from E. littorale has been described. The present review proposed that swertiamarin may be biosynthesized by the mevalonate or nonmevalonate pathways, followed by the seco-iridoid pathway. It has also been found that swertiamarin is a potent compound with diverse pharmacological activities, including hepatoprotective, analgesic, anti-inflammatory, antiarthritis, antidiabetic, antioxidant, neuroprotective and gastroprotective activities. The anticancer activity of swertiamarin against different cancer cell lines has been recently reported. The underlying mechanisms of all these pharmacological effects are diverse and seem to involve the regulation of different molecular targets, including growth factors, inflammatory cytokines, protein kinases, apoptosis-related proteins, receptors and enzymes. Swertiamarin also modulates the activity of several transcription factors, and their signaling pathways in various pathological conditions are also discussed. Moreover, we have highlighted the toxicity profile, pharmacokinetics and possible structural modifications of swertiamarin. The pharmacological activities and therapeutic potential of swertiamarin have been extensively investigated. However, more advanced studies are required including clinical trials and studies on the bioavailability, permeability and administration of safe doses to offer swertiamarin as a novel candidate for future drug development.Keywords: swertiamarin, Enicostemma littorale, biosynthesis, metabolic pathway, molecular targets, inflammatory cytokines

Harnessing the power of vortices shed in the wake of bluff bodies is indeed a boon to society in the face of fuel crisis. This fact serves as an impetus to develop a device called a hydro vortex power generator (HVPG), comprised of an elastically mounted cylinder that is free to oscillate in the cross-flow (CF) direction even in a low velocity flow field. The oscillatory motions in turn can be converted to useful power. This paper addresses the influence of system characteristics viz. stiffness ratio (k*) and mass ratio (m*) on the maximum response amplitude of the elastically mounted cylinder. Computational fluid dynamics (CFD) simulations have been used here to solve a two way fluid–structure interaction (FSI) problem for predicting the trend of variation of the non-dimensional amplitude Y/D with reduced velocity Ur through a series of simulations. Maximum amplitude motions have been attributed to the lowest value of m* with Ur = 8. However, the maximum lift forces correspond to Ur = 4, providing strong design inputs as well as indicating the best operating conditions. The numerical results have been compared with those of field tests in an irrigation canal and have shown reasonable agreement.

The kinetics of oxidation of a number of meta- and para-substituted N,α-diphenylnitrones (nitrone) by dichloramine-T (DCT) was investigated in the presence of alkali in aqueous acetonitrile medium. The order with respect to DCT was one and to OH- an inverse fractional order. The reaction was first order with respect to nitrone. Both electron releasing and withdrawing substituents suppress the reaction rate. The observed rate constant for the substituents were plotted against the Hammett constant, σ, and a non-linear concave downward curve was obtained. The electron withdrawing substituents fall on one side of the curve, having a negative ρ value and the electron releasing substituents fall on the other side, with a positive ρ value. A mechanism is proposed and the derived rate law is in conformity with the observed results.

Background: Thalassemia is a genetic blood disorder in children that results in the production of abnormal hemoglobin, leading to severe anemia and the need for frequent blood transfusions. Without proper management, these transfusions can cause iron overload in the body, which can damage vital organs such as the heart and liver. Therapy with oral iron chelators is crucial for these children, as it helps to remove the excess iron and prevent potential complications. The aim of this study was to assess and compare the effectiveness and safety of oral iron chelators, both when administered alone and in combination, in children with thalassemia who receive several blood transfusions. Materials and Methods: The study was carried out in the Department of Pediatrics, Sri Balaji Medical College and Hospital, over a period of ¬¬¬¬24 months. The study included 75 children with thalassemia who had undergone several transfusions and were receiving daily treatment with iron chelation. Results: The current study included 75 children with thalassemia who had received multiple blood transfusions. For duration of 12 months, they received daily iron chelation therapy with either deferiprone alone (Group 1), deferasirox alone (Group 2), or a combination of the two (Group 3). The serum ferritin levels were found to be reduced in all 3 groups, however the difference was not significant. The hepatic T2- MRI values had increased from baseline to folloup, however the difference was significant only in Group 3. The reduction of cardiac T2* MRI value was significantly reduced in Group 3 from baseline to follow-up. Conclusion: This study concluded that deferiprone and deferasirox were effective and safe when administered alone in children with thalassemia who had received several transfusions. [ABSTRACT FROM AUTHOR]