Current Topics in Medicinal Chemistry - Online First
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101 - 115 of 115 results
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Carbonic Anhydrase IX and Cyclooxygenase-2 Regulation in Renal Cell Carcinoma and Impact on Therapeutic Efficiency of Anti-CAIX CAR T cells
Available online: 27 June 2025More LessBackgroundClear cell renal cell carcinoma (ccRCC) is the most prevalent of renal cancers, with a 5-year survival rate of less than 10% for metastatic cases. The most efficient current strategies to treat ccRCC in advanced settings slightly increase progression-free survival. Chimeric antigen receptor T cells (CAR T cells) targeting carbonic anhydrase IX (CAIX) have reemerged as a promising alternative to ccRCC treatment based on recent preclinical data. CAIX and cyclooxygenase-2 (COX-2) are key players in tumor progression across various malignancies, overexpressed in 95% and 50% of ccRCC cases, respectively.
MethodsThis study employed in silico analysis to examine the expression of CAIX and COX-2 in ccRCC cell lines. The effects of celecoxib, anti-CAIX monoclonal antibodies, and anti-CAIX CAR T cells were evaluated using immunofluorescence microscopy and flow cytometry techniques.
ResultsHerein, we show a positive correlation between CAIX and COX-2 expression in ccRCC cell lines in vitro and in silico. Notably, COX-2 blockade with celecoxib led to a significant downregulation of CAIX expression in ccRCC cell lines. This effect is retroactive since treatment of these ccRCC cells with two different anti-CAIX monoclonal antibodies (mAbs) resulted in the downregulation of COX-2 expression. The association of celecoxib with anti-CAIX CAR T cell therapy impaired their cytotoxic potential over ccRCC in vitro, depending on CAIX cellular density.
ConclusionThese findings suggest a regulatory interaction between CAIX and COX-2 levels, indicating that COX-2 inhibitors may diminish the efficacy of CAIX-targeted therapies and should be avoided in combination treatments.
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A Review on Anticancer Potential and Structure-Activity Relationships (SAR) of Novel EGFR/HER2 Inhibitors
Authors: Subhadip Maity, Priya Devi, Aastha Singh, Vikas Asati and Vivek AsatiAvailable online: 20 June 2025More LessHuman Epidermal Growth Receptor (HER) plays an important role in cell signalling pathways and influences different cell functioning like angiogenesis, apoptosis, metastasis, and growth of cells. Their family includes four members with structural similarities, named EGFR/HER1, HER2, HER3, and HER4. Overexpression of these receptors is responsible for the development of cancer. EGFR/HER2 dual inhibitors, approved by the US FDA (Food and Drug Administration), include lapatinib, afatinib, neratinib, dacomitinib, etc., but these drugs lack selectivity, specificity, and undesirable adverse effects. The ultimate challenges in developing lead compounds for EGFR/HER2 dual inhibitors include achieving precision, and minimising toxicity and drug resistance. This inspires medicinal and organic chemists to design new molecules. The present manuscript focuses on the identification and development of therapeutic molecules that can inhibit the target proteins EGFR/HER2 and can further be used for the treatment of breast and lung malignancies. It also highlights the development of EGFR/HER2 dual inhibitors that belong to different structural classes like pyrimidine, quinazoline, pyridine, benzimidazole, and quinoline etc. Various parameters, such as Structure-Activity Relationships (SAR), clinical trials data, patent filed, and the molecular docking study of the most potent compounds provide a valuable asset for further designing and discovering new EGFR/HER2 dual inhibitors with potential therapeutic significances for cancer treatment.
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The Green Synthesis of Cu Nanoparticles and Investigation of the Antibacterial Properties and Cytotoxicity on Multidrug-Resistant E. coli
Authors: XiaoFeng Yuan and Yu WangAvailable online: 13 June 2025More LessIntroductionAlthough E. coli is considered a normal human microbiota, it may cause life-threatening infections such as septicemia, urinary tract infections, and enteric infections. Moreover, multidrug-resistant strains are a serious challenge in the clinic due to high mortality rates and the limited number of therapeutic options. Hence, the current study aimed to benefit from pink rose petals as a source of green synthesis of copper nanoparticles (Cu-NPs), to investigate the antibacterial features against multidrug-resistant E. coli, and to measure the cytotoxicity of Cu-NPs.
MethodsPink rose petals were used as a reducing agent for Cu-NP synthesis, and then XRD, zeta potential, UV-Vis, FTIR, SEM, and DLS analyses were performed to characterize the synthesized NPs. Moreover, the MIC and zone of inhibition values of Cu-NPs were measured and compared to common antibiotics. Additionally, the MTT assay was performed to assess the cytotoxicity.
ResultsThe green synthesized Cu-NPs were spherical and uniform with a size of ~200 nm. The MIC of Cu-NPs was 1024 μg/ml on the MDR strain of E. coli, representing the antibacterial activity comparable to levofloxacin (p-value>0.05) but less than imipenem and trimethoprim (p-value<0.001). Moreover, the CC50 of synthesized Cu-NPs was 731.2 μg/ml and significantly lower than the studied antibiotics (p-value<0.001).
ConclusionThe findings may suggest Cu-NPs as a promising antibacterial strategy against MDR strains of E. coli, however, further studies are encouraged to clarify the safety of optimized doses.
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A Review of Research from 2012 to 2024 on Pyrazole-based Anticancer Agents with SAR Study
Authors: Deepali Wanode, Deweshri Nandurkar, Megha Ambatkar, Nilesh Rarokar and Pramod KhedekarAvailable online: 10 June 2025More LessThe field of cancer research has witnessed a surge in the exploration of novel therapeutic agents, with pyrazole derivatives emerging as promising candidates in the quest for effective anticancer treatments. This comprehensive review provides an in-depth analysis of the research landscape surrounding pyrazole derivatives as potential anticancer agents over the period from 2012 to 2024. Many synthetic pyrazole derivatives have been approved by the FDA and used as chemotherapeutic medicines, and some are under clinical trials, also reported in this article. The review aims to serve as a valuable resource for researchers, guiding future investigations and fostering the development of innovative pyrazole-based anticancer therapeutics.
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Unraveling Neurodegenerative Disorders: The Potential of Indole and Imidazole-Based Heterocycles
Available online: 02 June 2025More LessNeurodegenerative diseases present a considerable challenge to healthcare systems worldwide, prompting the exploration of innovative treatment strategies. Heterocyclic compounds, specifically those originating from the indole and imidazole structures, have garnered increasing interest due to their potential to protect neurons. Based on an in-depth literature survey, this review explores the Structure-Activity Relationship (SAR) and pharmacokinetics to reveal the active pharmacophores of various indole and imidazole analogs. We delve into the underlying molecular and cellular mechanisms involved in neurodegeneration, highlighting how indole and imidazole derivatives exert neuroprotective effects by modulating oxidative stress, inflammation, protein misfolding, inhibiting cholinesterase, and neuroinflammation. Finally, we address the challenges and prospects in translating these findings into clinical therapies, underscoring the need for continued research to optimize the safety and efficacy of heterocyclic compounds in the treatment of neurodegenerative disorders.
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Prescription FINO2 and Pirfenidone Supported in Reducing Fibrosis in Mouse Breast Tumor Tissue by Targeting SLC7A11 and HMOX1
Available online: 29 May 2025More LessBackgroundBreast cancer has become the most commonly diagnosed cancer worldwide and represents a major burden to public health. Advances in understanding ferroptosis pathways and identifying new therapeutic targets raise hope for using ferroptosis modulators to treat untreatable diseases.
MethodsIn this study, BALB/c mice were divided into several groups: model, Doxorubicin-treated, FINO2-treated, Pirfenidone-treated, and a combined Pirfenidone + FINO2 group. After treatment, we assessed iron content in cancer cells, fibrosis area, CD34 expression, and mRNA levels of solute carrier family 7 member 11(SLC7A11) and heme oxygenase 1 (HMOX1).
ResultsResults showed that the average tumor size in the Pirfenidone + FINO2 group was significantly smaller than in the doxorubicin group. Treatments with FINO2, Pirfenidone, or their combination significantly increased iron content in cancer cells and reduced the fibrosis area. Co-treatment with FINO2 and Pirfenidone also led to notable decreases in CD34 expression and mRNA levels of SLC7A11 and HMOX1.
ConclusionThese findings suggest that FINO2 ferroptosis agonists, when combined with other anticancer agents like Pirfenidone, can enhance ferroptosis and reduce tumor fibrosis. Additionally, the overexpression of SLC7A11 and HMOX1 in breast cancer model mice is associated with increased tumor growth and reduced metastasis, indicating that targeting these proteins with specific inhibitors may be a promising strategy for breast cancer treatment.
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Design, Synthesis, Molecular Docking, and Biological Evaluation of 7-Phenyl-5-(thiophen-2-yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones as Antibacterial Agents
Available online: 26 May 2025More LessBackgroundNew antibacterial agents are urgently needed as bacterial diseases, especially urinary tract infections (UTIs), are becoming more common, and antibiotic resistance is increasing.
AimsThis study aimed to design, synthesize, and conduct molecular docking and biological evaluation of pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones as antibacterial agents.
Methods7-Phenyl-5-(thiophen-2-yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones were designed using an in silico approach. The designed compounds were synthesized using reported procedures. Molecular docking studies were carried out using the Maestro 12.9 module of Schrodinger software. QikProp module of the Schrodinger suite was used for in silico ADME evaluation of synthesized compounds. In vitro antibacterial activity of these compounds was assessed using the serial dilution method.
ResultsCompounds MA-03 and MA-12 showed potent antibacterial activity with MIC values of 1.56, 3.125, 1.56, and 6.25 µg/ml and 1.56, 3.12, 6.25, and 3.12 µg/ml, respectively, against Bacillus subtilis, Staphylococcus aureus, Pseudomonas putida, and Escherichia coli using controls ciprofloxacin and amoxicillin (0.78, 0.39, 1.56 and 0.39 µg/ml and 0.78, 3.125, 3.125, and 1.56 µg/ml). All the synthesized compounds demonstrated higher binding affinities against bacterial proteins with reference to amoxicillin and ciprofloxacin.
ConclusionAll the compounds exhibited antibacterial activity against all the tested strains of bacteria with optimum ADME profile.
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Highlighting the Therapeutic Potential of an Underexplored Target: Human Dihydroorotate Dehydrogenase in Cancer, Rheumatoid Arthritis and Sclerosis
Authors: Shubham Dash, Rupali Verma, Shorya Thakur, Gurvinder Singh and Charanjit KaurAvailable online: 23 May 2025More LessIntroductionThe dihydroorotate dehydrogenase (DHODH) enzyme plays a crucial role in the de novo pyrimidine biosynthesis pathway, catalysing the conversion of dihydroorotate to orotate in the cells. This pathway is important for the synthesis of nucleic acids and vital molecules essential for homeostasis, cellular functioning, and survival. So, targeting this enzyme can be an effective approach for the treatment of cancer, arthritis, malaria, viral or microbial infections, and other autoimmune diseases.
MethodsIn this review, we have highlighted the therapeutic implications of DHODH inhibition in cancer, rheumatoid arthritis and multiple sclerosis through an extensive literature survey from various scientific databases like PubMed, Google Scholar, Science Direct, Embase, clinical trials.gov.in, Google Patents, etc.
ResultsWe have tried to identify the pharmacophores from synthetic, phytochemical, and microbial origins, effective as DHODH inhibitors. The effect of structural changes on activity has been summarised, providing insights into the efficacy and mechanisms of these inhibitors at the molecular level. Furthermore, this review also presents a comprehensive analysis of clinical trials and patents related to DHODH inhibition to extract the valuable information to be used for clinical drug development in cancer, rheumatoid arthritis, and multiple sclerosis.
ConclusionBy integrating data from synthetic, plant, and microbial sources, along with clinical trial and patent outcomes, this review highlights the diverse role of DHODH. Its inhibition offers a more targeted approach to reduce the proliferation of rapidly dividing cells while sparing normal cells, modulating specific immune responses. But, limiting understanding of resistance mechanisms and potential for toxicity are the current challenges. It offers a roadmap for future research and drug discovery endeavours focused on harnessing the beneficial potential of DHODH inhibition, including the development of novel inhibitors with improved selectivity and pharmacokinetics across a wide array of pathological conditions.
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Structure-Guided Development of Mycobacterial Thymidine Monophosphate Kinase (MtbTMPK) Inhibitors: Unlocking New Frontiers in Tuberculosis Research
Available online: 21 May 2025More LessResearchers are actively engaged in developing new antitubercular drugs targeting the enzyme Mycobacterial Thymidine Monophosphate Kinase (MtbTMPK). This newer target has specificity and selectivity over other thymidylate kinases and especially differs from human thymidylate kinase (hTMPK). Over the last two decades, various potent MtbTMPK inhibitors comprised of both nucleoside and non-nucleoside structures have been developed. Mostly, nucleoside inhibitors have encountered substantial challenges, primarily related to poor solubility and permeability, which often render them inactive in whole-cell antitubercular assays. Consequently, the focus has shifted towards identifying potent non-nucleoside inhibitors that demonstrate activity in whole-cell assays. Researchers have employed structure-based modifications and leveraged insights from co-crystal structures of Mycobacterium tuberculosis TMPK (MtbTMPK) with its natural substrate, thymidine monophosphate (TMP), to develop potent non-nucleoside inhibitors—such as cynopyridone and 5-methylpyridine analogues—which have demonstrated nanomolar enzyme inhibitory activity. However, the problem was persistent and only a few non-nucleoside inhibitors have been found to be active in whole-cell activity, likewise nucleoside inhibitors. The reason behind the uncertainty between enzyme inhibitory and whole cell antitubercular activity of developed inhibitors remains incomprehensible to date, even though the efflux pump and permeability-related studies have been performed. Despite numerous efforts, no antitubercular drug targeting MtbTMPK has reached the market or clinical trials, though some non-nucleoside inhibitors are in preclinical stages. As MtbTMPK is crucial for Mycobacterium tuberculosis survival and its inhibition effectively reduces the growth of the bacteria, making it a promising target for novel antitubercular drugs. In addition to thymidine-like core structures, several inhibitors with non-thymidine-like cores have also been developed as potent MtbTMPK inhibitors, opening new opportunities for future research to explore the uncharted chemical space of this target.
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Traditional Chinese Medicines for Alzheimer's Disease: Current Knowledge, Clinical Applications, and Future Directions
Authors: Yu Deng, Chaojun Chen, Hongtao Li, Tianle Wang, Xu Zhang, Xueyang Wang and Guangtao PanAvailable online: 12 May 2025More LessAlzheimer's disease (AD) is a prevalent neurodegenerative disorder that poses a significant challenge to the health of the global aging population. Despite extensive research, the complex mechanisms underlying AD pathogenesis remain largely elusive. In recent years, a growing number of clinical studies have demonstrated the preventive and therapeutic potential of Traditional Chinese Medicine (TCM) against AD through multiple pathways, targets, and compounds. In this study, we conducted a review of the literature published over the past 20 years through international and domestic databases, including PubMed, Medline, Cochrane Library, CNKI, SinoMed, Wanfang, and VIP Journal Integration Platform. This review systematically evaluates current research advancements regarding single-herb preparations, bioactive constituents, and compound formulations in Traditional Chinese Medicine (TCM), with focused analysis on three therapeutic categories: tonifying herbs, blood-activating and stasis-eliminating agents, as well as orifice-opening, phlegm-resolving, and mind-stabilizing medicinal substances. Furthermore, this review discusses the potential mechanisms underpinning the anti-AD effects of TCMs. By integrating these insights, this review aims to establish a theoretical foundation for the application of TCMs in AD treatment and provide a reference for future pharmacological studies and the development of health-related products.
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Targeting Cell Signalling Pathways with New Small Molecules in Inflammation and Cancer
Authors: Ritam Mondal, Kalpana Rahate and Sandhya ChaudharyAvailable online: 12 May 2025More LessIn the treatment of cancer and inflammation, small molecules become powerful therapeutic tools that provide new therapeutic approaches with improved efficacy and fewer side effects. This review offers a thorough summary of current developments in small-molecule drugs that target cancer and inflammatory pathways. Specifically, inhibition of phosphodiesterase-4 (PDE4) and COX receptors have demonstrated potential in the field of inflammation to help mitigate a variety of inflammatory disorders. We examine the structural design, mechanism of action, and therapeutic potential of innovative small compounds that inhibit or alter these pathways. Significant attention is placed on the dual anti-inflammatory and anti-cancer properties of these substances. The evaluation emphasizes preclinical and clinical data, revealing the most promising candidates under development. In summary, the precise manipulation of cellular signalling pathways by small compounds constitutes a dynamic domain with the capacity to revolutionize therapeutic approaches for inflammation and cancer. Ongoing investigation of these chemicals is essential for the advancement of safer and more efficacious therapies.
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Integrative Analysis Reveals Genes Causal Relation with Ovarian Cancer and aging
Authors: Lan-hui Qin, Chongze Yang, Rui Song, Pei-yin Chen, Zijian Jiang, Weihui Xu, Guanzhen Zeng, Jin-yuan Liao and Liling LongAvailable online: 09 May 2025More LessBackgroundExploring the correlation between ovarian cancer and aging has great significance for understanding the pathogenesis of ovarian cancer and formulating targeted therapeutic regimens.
ObjectiveThis computational study aims to identify and validate key genes in monocyte subtypes related to ovarian cancer and aging, exploring potential causal relationships.
MethodsWe collected single-cell RNA sequencing data (GSE157007, GSE184880), GWAS data (14,049 samples and 40,941 controls from a European population), and eQTL data of ovarian cancer and aging. Using R software packages like Seurat and singleR, we conducted data integration, quality control, cell classification, and differential gene expression analysis to identify intersecting monocyte subtype genes in ovarian cancer and aging. We employed summary data-based Mendelian randomization (SMR) analysis and Heterogeneity in Dependent Instruments (HEIDI) tests to pinpoint causal genes. Further single-cell functional analyses (gene switching, cell communication, metabolic pathway analysis), Bulk RNA sequencing validation, functional enrichment, and protein-protein interaction (PPI) analyses elucidated these genes' biological roles.
ResultsThe dataset included 123,280 cells, revealing differential gene expression in classical monocytes (104 genes), intermediate monocytes (43 genes), and myeloid dendritic cells (39 genes). SMR and HEIDI identified causal relationships for 7 genes in classical monocytes, 3 in intermediate monocytes, and 3 in myeloid dendritic cells with ovarian cancer. Bulk RNA seq validation confirmed six monocyte genes as causal in ovarian cancer and aging. TREM1, SERPINB2, and CD44 were upregulated, while DST was downregulated; SLC11A1 and PNRC1 showed contradictory patterns. Interactions with NK and T cells involved LGALS9 - CD44/45 receptors. Riboflavin metabolism was a common enriched pathway.
ConclusionThis study identified six specific monocyte genes as potential therapeutic targets for ovarian cancer and aging.
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Optimization, Preparation, and Cytotoxic Potential of Pyrus communis Extract Loaded Ethosomes on Skin Cancer Cell Lines
Authors: Kiran Kangra, Vandana Garg, Anju Dhiman and Rohit DuttAvailable online: 02 May 2025More LessBackgroundSkin cancer is one of the most prevalent cancers globally and is considered a serious public health problem associated with high death rates. The current therapeutic regimes for skin cancer are limited by their low bioavailability, generation of resistance, or adverse side effects. Many fruit extract-based nutraceuticals hold potential as topical treatment methods. Pyrus communis (Pear) fruit extract is a rich source of cholinergic acid, presently used as therapy for various skin diseases. Thus, it qualifies as a promising candidate for skin cancer treatment.
ObjectiveThe objective of the study is to evaluate the cytotoxicity of Pyrus communis extract entrapped in ethosomes.
MethodsIn this study, Pyrus communis fruit extract was formulated in ethosomes using the hot method and optimized using central composite design. The optimized ethosomes were characterized in vitro for particle size distribution, zeta potential, entrapment efficiency, morphology, and particle stability.
ResultsPreliminary phytochemical screening results suggest that PCHE contains a significant amount of phenolic compounds compared to other extracts (PCEA and PCAE). The presence of these phenolic compounds contributes to the strong antioxidant and cytotoxic effects of PCHE, which are observed in a dose-dependent manner. Analysis through GC-MS has identified chlorogenic acid, arbutin, ursolic acid, quercetin, and epicatechin are present in PCHE. Based on the initial testing of the extracts, PCHE was chosen for the preparation of ethosomes. The optimized ethosomes were found to have a particle size of 699 nm and a zeta potential of -16.07. Transmission Electron Microscopy illustrated a closed, spherically symmetrical structure of the ethosomes. Additionally, the Franz diffusion cell analysis for percutaneous absorption using egg membrane indicated a steady-state flux of the drug from the ethosomes. The formulation's cytotoxicity potential was assessed using the epidermoid carcinoma cell line (A431) through the MTT assay. The results show that the ethosome formulations exhibit cytotoxic activity better than PCHE extract. 1
ConclusionIn sum, the result of this study clearly points out that Pyrus communis extract entrapped in ethosomes, prepared by hot method, displayed a cytotoxic potential against skin cancer cell lines. This ethosomal formulation can be harnessed for skin cancer therapy through further mechanistic analysis and animal studies.
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Laccaic Acid A: A Natural Anthraquinone with Potent Anticancer Activity against MDA-MB-231 Cells
Authors: Pankaj Dagur, Suddhasattya Dey, Rajdeep Dey, Hardik Bhatt and Manik GhoshAvailable online: 04 April 2025More LessBackground/AimThis study aims to isolate and evaluate the anticancer potential of laccaic acids from lac dye by utilizing polarity-based fractionation and high-performance liquid chromatography (HPLC).
MethodsIn this study, polarity-based fractionation of lac dye was performed to isolate its constituents. A novel HPLC method was developed for the chromatographic separation of lac dye components, utilizing gradient elution with two solvents: 0.1% (v/v) formic acid in LCMS-grade water (A) and 90:10 acetonitrile HPLC-grade (B) at a flow rate of 0.4 mL/min. This method facilitated the isolation of four key constituents: laccaic acid D, laccaic acid B, laccaic acid C, and laccaic acid A.
ResultsThe purity of these compounds was confirmed via LCMS methods. The anticancer activity of the isolated constituents was evaluated against the MDA-MB-231 cell line using the MTT assay. Notably, laccaic acid A demonstrated significant anticancer activity with an IC50 value of less than 100 nM, comparable to that of Adriamycin. Further investigations into the apoptotic activity of laccaic acid A were conducted using flow cytometry, revealing that laccaic acid A is a non-necrotic and apoptotic inducer. Additionally, considering that an effective anticancer agent may also exhibit antioxidant, anti-inflammatory, and anti-angiogenesis properties, the isolated laccaic acids were accessed for these biological activities.
ConclusionThe results were promising, indicating that laccaic acids could offer a multifaceted approach to cancer treatment. This study highlights the potential of laccaic acids as valuable candidates for anticancer therapy and warrants further investigation into their mechanisms of action and therapeutic efficacy.
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Triazole scaffold-based DPP-IV Inhibitors for the management of Type-II Diabetes Mellitus: Insight into Molecular Docking and SAR
Available online: 31 October 2024More LessDiabetes mellitus, characterized as a chronic metabolic disorder or a polygenic syndrome; is increasing at a very fast pace among every group of the population worldwide. It arises due to the inability of the body to produce enough insulin (the hormone responsible for controlling blood sugar levels) or inability to utilize the insulin, leading to hyperglycaemic condition, which, if left uncontrolled gives rise to chronic microvascular and macrovascular complications like retinopathy, neuropathy, nephropathy, coronary artery disease, cognitive impairment, etc. Several therapeutic approaches are available for the treatment of diabetes; among which dipeptidyl peptidase (DPP-IV) inhibitors (gliptins) hold a significant place. DPP-IV is a multifunctional enzyme or a serine exopeptidase that plays an imperative role in cleaving bioactive molecules. DPP-IV causes the breakdown of incretin hormone (GLP-1: Glucagon-like peptide 1 and GIP: Glucose-dependent insulinotropic peptide) that is essential for controlling glycaemic levels in the body. Inhibition of DPP-IV enzyme (DPP-IV inhibitors: Sitagliptin, Saxagliptin, Linagliptin, Alogliptin) prevents this breakdown, thereby controlling blood glucose levels and saving the patients from deleterious effects of prolonged hyperglycaemic conditions. Triazole-based DPP-IV inhibitors are a significant class of drugs used to treat Type 2 diabetes mellitus in a dose-dependent manner. Clinical trials have demonstrated their efficacy as monotherapy or in combination with other antidiabetic agents. This review highlights the molecular docking studies and structure-activity relationship of potential synthetic derivatives that may act as lead molecules for future drug discovery and yield drug molecules with enhanced efficacy, potency and reduced toxicity profile.
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