Manikanta Murahari

Koneru Lakshmaiah Education Foundation | KLU · School of Pharmacy

Cervical Cancer is a serious health concern possessing a serious health problem in women. This chapter provides a comprehensive overview of the role of biosimilars in Cervical Cancer (CC) by highlighting the global public health issue posed by CC and the urgent need for affordable and accessible treatment options. Biosimilars are biological product...

The immune checkpoint LAG-3 (lymphocyte activation gene 3) or CD223/FDC protein is located on chromosome 12 of the human genome. Enhancement of antitumor response is by modulation of signaling pathways between T lymphocytes and antigen-presenting cells and reestablishment of cytotoxic T lymphocyte activity. In recent years, LAG-3 has been taken int...

Telomerase is a well-recognised and a promising target for cancer therapy. In this study, we selected ligand-based approaches to design telomerase inhibitors for the development of potent anticancer agents for future cancer therapy. Till date no telomerase inhibitors have been clinically introduced. To investigate the chemical characteristics requi...

An innovative series of N‐substituted piperazine‐linked imidazothiazole derivatives 7(a–x) were synthesized, and their antitubercular effectiveness was evaluated. A three‐step reaction sequence involving the condensation of 1,3‐dichloroacetone and thiourea, coupling with substituted piperazines to give the intermediates 5(a–d) and cyclization with...

This publication is based on peer-reviewed manuscripts from the 2022 Conference on Current Trends in Drug Discovery, Development and Delivery (CTD4-2022) held at KL University, India. Providing a wide range of up to date topics on the latest advancements in drug design and discovery technologies, this book ensures the reader receives a good underst...

Huge fiscal investments in conjunction with high attrition rates encountered during de novo drug discovery delay the timelines required for development and entry of novel drug molecules into the pharmaceutical market. This situation mandates the initiation of contemporary drug repurposing research strategies to reconnoiter the hidden off-label indi...

NS3-4A, a serine protease, is a primary target for drug development against Hepatitis C Virus (HCV). However, the effectiveness of potent next-generation protease inhibitors is limited by the emergence of mutations and resulting drug resistance. To address this, in this study a structure-based drug design approach is employed to screen a large libr...

Alzheimer’s disease is characterized by amyloid-beta aggregation and neurofibrillary tangles. Acetylcholinesterase (AChE) hydrolyses acetylcholine and induces amyloid-beta aggregation. Acetylcholinesterase inhibitors (AChEI) inhibit this aggregation by binding to AChE, making it a potential target for the treatment of AD. In this study, we have foc...

Carboxymethyl chitosan-PVA crosslinked films were prepared and evaluated. The mechanism of crosslinking was proposed with analytical evidence. The prepared crosslinked films showed excellent cell compatibility and optimal antibacterial action. The prepared films exhibited migration of cells towards wound both during in-vitro and in-vivo studies.

The viral disease dengue is transmitted by the Aedes mosquito and is commonly seen to occur in the tropical and subtropical regions of the world. It is a growing public health concern. To date, other than supportive treatments, there are no specific antiviral treatments to combat the infection. Therefore, finding potential compounds that have antiv...

α-synuclein is the synaptic protein majorly involved in neuronal dysfunction and death and it is well known for the last two decades as a hallmark of Parkinson’s disease. Alpha-synuclein is involved in neurodegeneration mediated through various neurotoxic pathways, majorly including autophagy or lysosomal dysregulation, mitochondrial disruption, sy...

The apoptotic balance of the cell is governed by Bcl-2 protein family. Increased expression of pro-survival members of Bcl-2 family is indicative of cell death evasion and cancer metastasis. The current therapeutic approach to regulate the Bcl-2 overexpression using small molecule approach, although effective, is limited by dose related toxicity. I...

Fluoroquinolones are broad spectrum antibiofilm agents. Herein, synthesized are a series of hexafluoro functionalized quinoline‐3‐carboxylate derivatives (4 a–7 d) from aryl amines as novel chemotherapeutic agents. The compound ethyl 5‐chloro‐6‐(1,1,1,3,3,3‐hexafluoro‐2‐hydroxypropan‐2‐yl)‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylate (4 b) exhibited th...

The development of drug resistance and severe side-effects has reduced the clinical efficacy of the existing anti-cancer drugs available in the market. Thus, there is always a constant need to develop newer anti-cancer drugs with minimal adverse effects. Researchers all over the world have been focusing on various alternative strategies to discover...

Tuberculosis is a chronic communicable disease caused by Mycobacterium tuberculosis (Mtb) and spreads from lungs to lymphatic system. The cell wall of mycobacterium plays a prominent role in maintaining the virulence and pathogenicity and also acts as prime target for drug discovery. Hence, this study has put into emphasis with target MmpLs (Mycoba...

PurposeThe research focuses on the development and characterization of cross-linked carboxymethyl chitosan (CMCh)-gelatin-copper oxide (CuO) bioscaffolds for wound healing applications.Methods Freeze drying technique was used to develop four bioscaffolds using a two-stage cross-linking process and developed scaffolds were characterized using ATR FT...

Epidermal growth factor receptor (EGFR) is a validated drug target for cancer chemotherapy. Mutations in EGFR are directly linked with the development of drug resistance and this has led for the development of newer drugs in quest for more efficacious inhibitors. The current research is focused on identifying potential and safe molecules as EGFR in...

Schif bases are well-known compounds for having signifcant biological properties. In this study, a new Schif base ligand and its metal complexes were synthesized, and their antioxidant and enzyme inhibitory activities were evaluated. The new Schif base ligand was synthesized with the condensation reaction of 6-tert-butyl 3-ethyl 2-amino-4,5-dihydro...

Current study investigated the formation of binary and ternary inclusion complexes of Irbesartan (IRB) with Hydroxypropyl-β-Cyclodextrin (HP-βCD) as host and l-Arginine (L-Arg) as ternary agent. Inclusion complexes were characterized using solubility, invitro release, DSC and XRD studies. Host-guest interactions were explored by FTIR, ¹H NMR and mo...

Background and Objectives Overexpression of prosurvival Bcl-2 family members make tumor cells resistant to conventional cancer therapeutic agents. It is commonly observed feature in many different types of human tumors. Hence, small-molecules as Bcl-2 inhibitors may have a promising therapeutic potential for the treatment of human cancer. The given...

Hydroxychloroquine (HCQ) and its derivatives have recently gained tremendous attention as a probable medicinal agent in the COVID-19 outbreak caused by SARS-CoV-2. An efficient agent to act directly in inhibiting the SARS-CoV-2 replication is yet to be achieved. Thus, the goal is to investigate the dynamic nature of HCQ derivatives against SARS-CoV...

B-cell lymphoma 2 (BCL-2) family is one of the chief regulators of cellular apoptosis. The intricate interactions between pro-apoptotic and anti-apoptotic genes of the BCL-2 family dictate the apoptotic balance of the cell. An overexpression of the anti-apoptotic members of BCL-2 is indicative of cell death evasion and cancer metastasis. Among the...

Many plant species have a large diversity of secondary metabolites with different biological activities. This study aims to assess the phenolic constituent, enzyme inhibitory and antioxidant activities of the aqueous (water) and methanol extracts of Inula discoidea. The enzyme assays showed effective enzyme inhibition of the methanol extract agains...

Phenyl-3-(thiophen-2-yl)-1H-pyrazole-5-carboxamide derivatives were designed and evaluated for their in vitro enzyme inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione S-transferase (GST). In particular, N,1-diphenyl-3-(thiophen-2-yl)-1H-pyrazole-5-carboxamide (10) was found to be the best AChE...

Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that has been spreading across the globe. The World Health Organization (WHO) declared it as a public health emergency. The treatment of COVID-19 has been hampered due to the lack of effective therapeutic efforts. Main Protease (Mpro) is a key enzyme in the viral replication cycle a...

A series of Fe(II), Ni(II), and Pd(II) complexes were prepared with a novel Schiff base ligand containing pyridine moiety. The prepared compounds were characterized using FT-IR, ¹H and ¹³ C NMR, UV–Vis, powder XRD, thermogravimetric analysis, mass spectra, magnetic susceptibility, and elemental analysis. The coordination geometry of Fe(II) and Ni(I...

The novel coronavirus also referred to as SARS-CoV-2 causes COVID-19 and became global epidemic since its initial outbreak in Wuhan, China, in December 2019. Research efforts are still been endeavoured towards discovering/designing of potential drugs and vaccines against this virus. In the present studies, we have contributed to the development of...

Drug resistance is one of the critical challenges faced in the treatment of Glioma. There are only limited drugs available in the treatment of Glioma and among them Temozolomide (TMZ) has shown some effectiveness in treating Glioma patients, however, the rate of recovery remains poor due to the inability of this drug to act on the drug resistant tu...

Irbesartan (IRB), one of the extensively prescribed drugs, for treatment of hypertension has limited therapeutic potential attributed to its poor water solubility, slow dissolution rate and poor bioavailability. Cyclodextrin-based nanosponges (NSs) are novel nanosized delivery systems comprised of hyper-crosslinked solid nanoparticles with nanosize...

Introduction: The present study attempts to identify potential targets of H. pylori for novel inhibitors from therapeutic herb, mango ginger (Curcuma amada Roxb.). Methods: Crystal structure of all the selected drug targets obtained from Protein Data Bank (PDB) were subjected to molecular docking against a total of 130 compounds (found to have bio...

Melissa officinalis (Lamiaceae) was used to treat multiple human afflictions. Literary works demonstrated that it has many biological activities. Today's research aims to recognise Melissa officinalis phyto-derived anti-viral compounds against main protease and spike protein of COVID-19, to gain insight into the molecular interactions. In the curre...

Inula plant species have a large diversity of secondary metabolites with different biological activities. This study aims to assess the determination of phenolic constituent, enzyme inhibitory, and antioxidant activities of Inula discoidea (I. discoidea) aqueous and methanol extracts. The enzyme assays showed that the methanol extract of I. discoid...

Around the world, growth of lung cancer remains to be the most widely recognized reason for disease-related deaths. It is the second most common cancer observed in both men and women with a risk of 1 in 15 for men and 1 in 17 for women as per the statistical data of American Cancer Society. Probiotics are defined as “live microorganisms which, when...

In medicinal chemistry, nitrogen atom containing molecules have gained a lot of attention as they possess diverse biological properties. Dihydropyrimidinone is one such pharmacologically important molecule possessing several properties such as anti-bacterial, anti-fungal, anti-inflammatory, anti-oxidant, antipyretic, anti-depressant, anti-tumor etc...

Cell wall of mycobacterium acts as a primary interface which helps in the regulation of important functions and also aids to pathogenicity and virulence of the organism, making it a crucial target for drug discovery. Decaprenylphosphoryl-D-ribose 2’-epimerase (DprE), is important for the growth and survival of Mycobacterium tuberculosis. DprE1 is a...

Cinnamon has been utilized to remedy a lot of afflictions of humans. Literary works illustrate that it possesses numerous biological activities. Our research study is intended to recognize the phyto-derived antiviral substances from Cinnamon against COVID-19 main protease enzyme and to understand the in silico molecular basis of its activity. In th...

Cancer is one of the global prominent causes of death and foremost worldwide health concern. Despite unprecedented progress in cancer chemoprevention, vast number of cancers however remain an undefeatable challenge for treatment modalities. Immense therapeutic activities of puerarin contribute to its use in various health disorders. In this review,...

Target based drug design is increasingly gaining more attention for anticancer therapy. Telomere are repetitive nucleotide sequences that are present at the end of chromosomal DNA. Shortening of telomere length has been associated with cellular senescence and the aging process. In cancerous cell telomerase is activated which maintain the length of...

Alzheimer’s Disease (AD), a most prevailing neurodegenerative disorder with turbulence in cognitive and behavioural abilities, epitomizes one of the highest unmet medical requirements. The current AD treatment focuses merely on symptomatic relief, this explains a dearth in drug research oriented towards unwinding of disease specific druggable targe...

AIDS is a global infection involving several complications and its increasing prevalence every year has prioritized our study. Therapy associated with HIV has led to emergence of multidrug resistance and toxicity. Thus, the development of a potent, affordable and safe anti-HIV drug is a global concern. Among the different targets developed, inhibit...

Apoptosis is one of the major mechanisms exhibited in response to cell death and induction of apoptosis in tumour cells signifies a potential target for cancer therapy. Bcl-2 family proteins play a key role in regulation of the apoptotic pathway. Bcl-2 overexpression is commonly associated with various cancers including breast cancer, prostate canc...

Delivery of bisphosphonates like risedronate has been a major challenge till date due to its poor bioavailability and GIT adverse effects. In the present study, we explored the prospective use of risedronate functionalized chitosan nanoparticle (RISCN) for management and treatment of osteoporosis. The prepared nanoparticle was characterized by usin...

Acquired Immuno Defficiency Syndrome (AIDS) is one of the major global life threatening condition caused by Human Immunodeficiency Virus (HIV) and its prevalence has been increasing every year. Hence, this study has put its emphasis on HIV. Inhibition of Non-Nucleoside Reverse Transcriptase (NNRT) is considered as a well-developed target for HIV. S...

Drug latentiation is a process of modifying a drug molecule structurally to improve its binding affinity as well as increasing the drug–receptor interactions and potentiate its therapeutic potential. In the quest for discovering more potent epidermal growth factor receptor (EGFR) inhibitors, gefitinib‐based derivatives were designed by simple struc...

The design and synthesis of novel pyrazole based derivatives has been carried out using the ligand based approach like pharmacophore and QSAR modelling of reported pyrazoles from the available literature to investigate the chemical features that are essential for the design of selective and potent COX-2 inhibitors. Both pharmacophore and QSAR model...

Drug repurposing is an unconventional drug discovery approach to explore new therapeutic benefits of existing, shelved and the drugs in clinical trials. This approach is currently emerging to overcome the bottleneck constraints faced during traditional drug discovery in grounds of financial support, timeline and resources. In this direction, severa...

Cancer is one of the world's most pressing challenge to research community and leading cause of death. As per the 13 th report of American Science of Clinical Oncology, 14 million people are diagnosed with cancer every year. With the advancement of technology and relentless efforts of researchers, quality of life has improved with more cancer survi...

The present study demonstrates the solubility and dissolution enhancement of Efavirenz (EFV) through preparation of supramolecular inclusion complexes. The supramolecular system comprising of EFV, hydroxypropyl‑β‑cyclodextrin (HP-β-CD) and L‑Arginine was prepared by physical mixing and spray drying methods. The complexes were characterized by powde...

The present study demonstrated the binary and ternary complexes of Zaltoprofen (ZPF) with β-CD and HP-β-CD. The products were characterized using solubility, in vitro dissolution, DSC, and PXRD studies. The mode of interaction of guest and host was revealed through ¹H NMR and FT-IR studies. A significant increase was noticed in the stability consta...

In today's world of modern medicine and novel therapies, cancer still remains to be one of the prime contributor to the death of people worldwide. The modern therapies improve condition of cancer patients and are effective in early stages of cancer but the advanced metastasized stage of cancer remains untreatable. Also most of the cancer therapies...

Natural compounds have been attracting huge attention because of their broad therapeutic properties with specificity in their action in human health care as functional foods, pharmaceuticals and nutraceuticals. However poor bioavailability and reduced bioactivity attributed to poor solubility and instability is the major drawback hindering the inco...

The present investigation was aimed to prepare inclusion complexes of a therapeutically important nonsteroidal anti-inflammatory drug, etodolac (ETD) with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and to study the effect of l-arginine (l-Arg) as an auxiliary agent on the complexation efficiency of HP-β-CD to improve aqueous solubility and the disso...

PurposeThe objective of present study was to increase solubility and dissolution performance of a poorly water soluble antidiabetic drug, Nateglinide (NAT), through formation of inclusion complexes with hydroxypropyl-beta-cyclodextrin (HP–β–CD). The effect of L-arginine (ARG), an amino acid, on the complexation efficiency and solubility enhancing p...

Drug resistance in cancer is an unmet medical challenge and a major drawback for the failure of many chemotherapeutic drugs. Search for targeted, effective drug with minimum toxicity is an urgent need. Acridone which is an alkaloid derivative has been attributed as molecule in reversing drug resistance in cancer cells for a long time now. In the pr...

Recent studies have shown that certain genetically modified tumour cells are extremely sensitive to the effects of PARP-1 inhibition without the need for the presence of a cytotoxic agent leading to selective cell death. For example BRCA1 and BRCA2, which are components of the homologous recombination DNA repair pathway, are deleted in 5- 10% breas...

As advancements in the field of nanoparticle imaging science are made, one of the first use benefitswill be in open and endoscopic conditions. There is considerable evidence indicating that the use of injected contrast agents can improve the detection of tumor margins and small metastases. New and innovative targeting and contrast agents including...

In the present work quinazolinone derivatives (2b-k) were synthesized by N-alkylation of amine of 2-aminobenzamide using chloroacetylchloride in the presence of triethylamine produced intermediate a-chloro amide which upon cyclisation in the presence of triethylamine produced intermediate 2-chloromethyl quinazolinone (1). Formation of 1 was confirm...