Research Title: An insight on synthetic and medicinal aspects of pyrazolo[1,5-a]pyrimidine scaffold

Author: Balakumar Chandrasekarn, Published Year: 2017

European Journal of Medicinal Chemistry, 126

Faculty: Pharmacy

Abstract: Pyrazolo[1,5-a]pyrimidine scaffold is one of the privileged hetrocycles in drug discovery. Its application as a buliding block for developing drug-like candidates has displayed broad range of medicinal properties such as anticancer, CNS agents, anti-infectious, anti-inflammatory, CRF1 antagonists and radio diagnostics. The structure-activity relationship (SAR) studies have acquired greater attention amid medicinal chemists, and many of the lead compounds were derived for various disease targets. However, there is plenty of room for the medicinal chemists to further exploit this privileged scaffold in developing potential drug candidates. The present review briefly outlines relevant synthetic strategies employed for pyrazolo[1,5-a]pyrimidine derivatives. It also extensively reveals significant biological properties along with SAR studies. To the best of our understanding current review is the first attempt made towards the compilation of significant advances made on pyrazolo[1,5-a]pyrimidines reported since 1980s.

Keywords: Pyrazolo[1,5-a]pyrimidineAnti-cancer agentsAnti-infectious agentsCNS agentsAnti-inflammatory agentsRadiopharmaceuticals

Research Title: Synthesis, antiproliferative activity and docking study of novel rhodanine derivatives as Bcr-Abl T1351 inhibitors

Author: Balakumar Chandrasekarn, Published Year: 2017

Research on Chemical Intermediates, 43

Faculty: Pharmacy

Abstract: A series of novel N-substituted rhodanines 6a–g were synthesized by a microwave synthesizer, and evaluated for their anti-proliferative activity. Most of the compounds showed inhibition against K562 cells in a dose-dependent manner and in particular compounds 6a, 6b and 6f exhibited most potent activity with an IC50 value of 19.62, 24.01 and 22.91 µg/ml by MTT assay. Further in silico docking studies of the above compounds against Bcr-Abl T1351 protein showed good binding affinity, thus indicating that the compounds behave as third generation inhibitors. A dose-dependent increase in LDH release upon treatment with 6a–g complements the MTT assay for anti-proliferative activity. Flow cytometry of 6a showed that it interferes with the cell division by indicating G1 phase arrest followed by apoptosis.

Keywords: Synthesis; antiproliferative activity; docking; rhodanine derivatives

Research Title: DEHYDROZINGERONE INSPIRED STYRYL HYDRAZINE THIAZOLE HYBRIDS AS PROMISING CLASS OF ANTI-MYCOBACTERIAL AGENTS

Author: Balakumar Chandrasekarn, Published Year: 2018

WCP2018 (18th World Congress of Basic and Clinical Pharmacology), Japan

Faculty: Pharmacy

Abstract: Tuberculosis (TB) is a chronic necrotizing bacterial infection caused by Mycobacterium tuberculosis (Mtb), which has been a bane of humanity for thousands of years and remains as one of the flourishing health problems in the world. The global resurgence of TB and development of drug resistance imposes for an imperative attention of medicinal chemists to develop innovative anti-mycobacterial agents as no new classes of anti-TB agents.

Keywords: DEHYDROZINGERONE INSPIRED STYRYL HYDRAZINE THIAZOLE HYBRIDS

Research Title: Phyto-Engineered Gold Nanoparticles (AuNPs) with Potential Antibacterial, Antioxidant, and Wound Healing Activities Under in vitro and in vivo Conditions

Author: Balakumar Chandrasekarn, Published Year: 2020

Phyto-Engineered Gold Nanoparticles (AuNPs) with Potential Antibacterial, Antioxidant, and Wound Healing Activities Under in vitro and in vivo Conditions, 15

Faculty: Pharmacy

Abstract: A diabetic ulcer is one of the major causes of illness among diabetic patients that involves severe and intractable complications associated with diabetic wounds. Hence, a suitable wound-healing agent is urgently needed at this juncture. Greener nanotechnology is a very promising and emerging technology currently employed for the development of alternative medicines. Plant-mediated synthesis of metal nanoparticles has been intensively investigated and regarded as an alternative strategy for overcoming various diseases and their secondary complications like microbial infections. Hence, we are interested in developing phyto-engineered gold nanoparticles as useful therapeutic agents for the treatment of infectious diseases and wounds effectively.

Keywords: gold nanoparticles, antibacterial, antioxidant, wound healing, in vivo mice model

Research Title: Neurological Consequences of SARS-CoV-2 Infection and Concurrence of Treatment-Induced Neuropsychiatric Adverse Events in COVID-19 Patients: Navigating the Uncharted

Author: Balakumar Chandrasekarn, Published Year: 2021

Frontiers in Molecular Biosciences, 8

Faculty: Pharmacy

Abstract: evere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor and invade the human cells to cause COVID-19-related pneumonia. Despite an emphasis on respiratory complications, the evidence of neurological manifestations of SARS-CoV-2 infection is rapidly growing, which is substantially contributing to morbidity and mortality. The neurological disorders associated with COVID-19 may have several pathophysiological underpinnings, which are yet to be explored. Hypothetically, SARS-CoV-2 may affect the central nervous system (CNS) either by direct mechanisms like neuronal retrograde dissemination and hematogenous dissemination, or via indirect pathways. CNS complications associated with COVID-19 include encephalitis, acute necrotizing encephalopathy, diffuse leukoencephalopathy, stroke (both ischemic and hemorrhagic), venous sinus thrombosis, meningitis, and neuroleptic malignant syndrome. These may result from different mechanisms, including direct virus infection of the CNS, virus-induced hyper-inflammatory states, and post-infection immune responses. On the other hand, the Guillain-Barre syndrome, hyposmia, hypogeusia, and myopathy are the outcomes of peripheral nervous system injury. Although the therapeutic potential of certain repurposed drugs has led to their off-label use against COVID-19, such as anti-retroviral drugs (remdesivir, favipiravir, and lopinavir-ritonavir combination), biologics (tocilizumab), antibiotics (azithromycin), antiparasitics (chloroquine and hydroxychloroquine), and corticosteroids (dexamethasone), unfortunately, the associated clinical neuropsychiatric adverse events remains a critical issue. Therefore, COVID-19 represents a major threat to the field of neuropsychiatry, as both the virus and the potential therapies may induce neurologic as well as psychiatric disorders.

Keywords: SARS-CoV-2; Neuropsychiatric Adverse Events

Research Title: Curcumin-Celecoxib: a synergistic and rationale combination chemotherapy for breast cancer

Author: Balakumar Chandrasekarn, Published Year: 2021

European Review for Medical and Pharmacological Sciences, 25

Faculty: Pharmacy

Abstract: Over-expression of COX-2 has been linked with various molecular signaling such as carcinogenesis, invasiveness, and malignant tumour metastasis. Besides, the use of celecoxib is also related to lowering the risk of breast cancer. This study therefore designed to explore the synergistic inhibitory effect of the combination of curcumin and celecoxib on the growth of human breast cancer cells.

Keywords: MDA-MB-231, Human breast cancer, Celecoxib, Curcumin, COX-2, Adjuvant molecule, Cytotoxicity, ADME/T

Research Title: Emerging therapeutic approaches to combat COVID-19: present status and future perspectives

Author: Balakumar Chandrasekarn, Published Year: 2021

Frontiers in Molecular Biosciences, 8

Faculty: Pharmacy

Abstract: Coronavirus disease (COVID-19) has emerged as a fast-paced epidemic in late 2019 which is disrupting life-saving immunization services. SARS-CoV-2 is a highly transmissible virus and an infectious disease that has caused fear among people across the world. The worldwide emergence and rapid expansion of SARS-CoV-2 emphasizes the need for exploring innovative therapeutic approaches to combat SARS-CoV-2. The efficacy of some antiviral drugs such as remdesivir, favipiravir, umifenovir, etc., are still tested against SARS-CoV-2. Additionally, there is a large global effort to develop vaccines for the protection against COVID-19. Because vaccines seem the best solution to control the pandemic but time is required for its development, pre-clinical/clinical trials, approval from FDA and scale-up. The nano-based approach is another promising approach to combat COVID-19 owing to unique physicochemical properties of nanomaterials. Peptide based vaccines emerged as promising vaccine candidates for SARS-CoV-2. The study emphasizes the current therapeutic approaches against SARS-CoV-2 and some of the potential candidates for SARS-CoV-2 treatment which are still under clinical studies for their effectiveness against SARS-CoV-2. Overall, it is of high importance to mention that clinical trials are necessary for confirming promising drug candidates and effective vaccines and the safety profile of the new components must be evaluated before translation of in vitro studies for implementation in clinical use.

Keywords: therapeutic approaches; COVID-19

Research Title: Computation in BioInformatics: Multidisciplinary Applications

Author: Balakumar Chandrasekarn, Published Year: 2021

Faculty: Pharmacy

Abstract: COMPUTATION IN BIOINFORMATICS Bioinformatics is a platform between the biology and information technology and this book provides readers with an understanding of the use of bioinformatics tools in new drug design. The discovery of new solutions to pandemics is facilitated through the use of promising bioinformatics techniques and integrated approaches. This book covers a broad spectrum of the bioinformatics field, starting with the basic principles, concepts, and application areas. Also covered is the role of bioinformatics in drug design and discovery, including aspects of molecular modeling. Some of the chapters provide detailed information on bioinformatics related topics, such as silicon design, protein modeling, DNA microarray analysis, DNA-RNA barcoding, and gene sequencing, all of which are currently needed in the industry. Also included are specialized topics, such as bioinformatics in cancer detection, genomics, and proteomics. Moreover, a few chapters explain highly advanced topics, like machine learning and covalent approaches to drug design and discovery, all of which are significant in pharma and biotech research and development. Audience Researchers and engineers in computation biology, information technology, bioinformatics, drug design, biotechnology, pharmaceutical sciences.

Keywords: BioInformatics; Multidisciplinary Applications

Research Title: Handbook on nanobiomaterials for therapeutics and diagnostic applications

Author: Balakumar Chandrasekarn, Published Year: 2021

Faculty: Pharmacy

Abstract: Handbook on nanobiomaterials for therapeutics and diagnostic applications

Keywords: Handbook on nanobiomaterials for therapeutics and diagnostic applications

Research Title: Perspectives on RNA Vaccine Candidates for COVID-19

Author: Balakumar Chandrasekarn, Published Year: 2021

Frontiers in Molecular Biosciences, 8

Faculty: Pharmacy

Abstract: With the current outbreak caused by SARS-CoV-2, vaccination is acclaimed as a public health care priority. Rapid genetic sequencing of SARS-CoV-2 has triggered the scientific community to search for effective vaccines. Collaborative approaches from research institutes and biotech companies have acknowledged the use of viral proteins as potential vaccine candidates against COVID-19. Nucleic acid (DNA or RNA) vaccines are considered the next generation vaccines as they can be rapidly designed to encode any desirable viral sequence including the highly conserved antigen sequences. RNA vaccines being less prone to host genome integration (cons of DNA vaccines) and anti-vector immunity (a compromising factor of viral vectors) offer great potential as front-runners for universal COVID-19 vaccine. The proof of concept for RNA-based vaccines has already been proven in humans, and the prospects for commercialization are very encouraging as well. With the emergence of COVID-19, mRNA-1273, an mRNA vaccine developed by Moderna, Inc. was the first to enter human trials, with the first volunteer receiving the dose within 10 weeks after SARS-CoV-2 genetic sequencing. The recent interest in mRNA vaccines has been fueled by the state of the art technologies that enhance mRNA stability and improve vaccine delivery. Interestingly, as per the “Draft landscape of COVID-19 candidate vaccines” published by the World Health Organization (WHO) on December 29, 2020, seven potential RNA based COVID-19 vaccines are in different stages of clinical trials; of them, two candidates already received emergency use authorization, and another 22 potential candidates are undergoing pre-clinical investigations. This review will shed light on the rationality of RNA as a platform for vaccine development against COVID-19, highlighting the possible pros and cons, lessons learned from the past, and the future prospects.

Keywords: RNA Vaccine; COVID-19