Research Title: Synthesis, pharmacological evaluation, and molecular modeling studies of novel isatin hybrids as potential anticancer agents

Author: Balakumar Chandrasekarn, Published Year: 2023

Journal of Saudi Chemical Society, 27

Faculty: Pharmacy

Abstract: A novel series of isatin hybrids 5a-g was designed, synthesized, and characterized spectroscopically. The synthesized compounds were evaluated for their cytotoxic activity against the human breast cancer cell line (MCF-7) by in vitro MTT assay. Amongst the tested compounds, 5e compound bearing benzyl moiety at N4 piperazine was found to be the most active with the promising IC50 (12.47 µM). Moreover, the active compounds 5e and 5g were subjected to antitumor evaluation (in vivo) against Dalton’s ascitic lymphoma (DAL) cell line and the results suggested that the best active compound 5e can normalize the blood picture in comparison to the standard drug. An in silico molecular docking study using the crystal structure of Hsp90 protein described the role of significant protein–ligand interactions and revealed more insights into the binding mode. The drug-likeliness of the compounds was predicted based on Lipinski's rule of five and pharmacokinetic ADME parameters. Hence, the synthesized isatin hybrids could be novel starting point anticancer lead compounds demonstrating drug-like properties which can be explored further for anticancer drug discovery.

Keywords: Isatin-pyrimidine hybridAntiproliferative activityBreast cancer cell (MCF-7)Dalton’s ascitic lymphoma (DAL)Molecular docking

Research Title: Development of a Polyherbal Topical Gel for the Treatment of Acne

Author: Balakumar Chandrasekarn, Published Year: 2023

GELS, 9

Faculty: Pharmacy

Abstract: The present work aimed to formulate and evaluate a polyherbal gel using Aloe barbadensis and extract of Vigna radiata for the treatment of acne, a disorder of the skin in which hair follicles and sebaceous glands are blocked, causing inflammation and redness of the skin. Aloe barbadensis pulp was collected and mixed with the extract of Vigna radiata and formulated into a gel using Carbopol 940, triethanolamine, and propylene glycol as the gelling agent, viscosity modifier, and pH modifier, respectively. The gel was evaluated for its antimicrobial properties against Staphylococcus aureus, Escherichia coli, and Candida albicans. Antimicrobial agents, such as gentamycin and fluconazole, were used as the standards. The developed formulation showed promising zone of inhibition. The gel was further evaluated for its physicochemical properties. The formulation showed a promising effect on acne together with the additive effect of Aloe barbadensis on skin.

Keywords: Aloe barbadensis; Vigna radiata; Carbopol 940; polyherbal gel; acne

Research Title: Topochemical studies on 4(3H)quinazolinones as dihydrofolate reductase (DHFR) inhibitors: An approach to predict the antitumour activity

Author: Balakumar Chandrasekarn, Published Year: 2013

International Journal of Medical & Pharmaceutical Sciences , 3

Faculty: Pharmacy

Abstract: Background of study: Inhibition of DHFR is one of the potential targets for anticancer therapy. In this study, topochemical descriptor based calculations were carried out on substituted 4(3H)-quinazolinones to predict DHFR inhibition. A data set of 50 molecules of substituted 4(3H)-quinazolinones as potential DHFR inhibitors and its topological descriptors like Wiener’s index, Balaban’s index and Molecular topological index were investigated. Objective: The topological data was systematically analyzed and suitable descriptor based topochemical models were developed after the identification of the active ranges. Research methodology: Subsequently, the DHFR inhibition activity was predicted for all the data set of molecules using topochemical models. Then, the predicted activity was compared with the experimentally reported DHFR inhibitor activity. Results: The overall prediction of DHFR inhibition was found to be higher accuracy of 80% for the models based on Wiener’s index as well as Molecular topological index and 74% for Balaban’s index. Conclusions: The prediction of DHFR inhibition using topochemical descriptors can be useful to design newer analogues of quinazolines as potential DHFR inhibitors.

Keywords: Dihydrofolate reductase, Wiener’s index, Balaban’s index, Molecular topological index and 4(3H)-quinazolinone, Antitumor action

Research Title: Antidiabetic activity of the aqueous extracts of Foeniculum vulgare on streptozotocin-induced diabetic rats

Author: Balakumar Chandrasekarn, Published Year: 2014

Int J Adv Pharm Biol Chem, 3

Faculty: Pharmacy

Abstract: Diabetes mellitus is a clinical syndrome associated with an abnormal high blood glucose concentration due to insufficient insulin secretion or defective in insulin action. The present study was attempted to evaluate the antidiabetic effects of Foeniculum vulgare in streptozotocin-induced diabetic rats.

Keywords: Antidiabetic activity; Foeniculum vulgare

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