PPARs (Peroxisome Proliferator-activated Receptors) and Their Agonists in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease leading to dementia because of complex phathomechanisms like amyloid ß (Aß) aggregation, tau aggregates, and neurofibrillary tangles. Peroxisome proliferator-activated receptor (PPAR) agonists have been reported recently with neuroprotective and anti-inflammatory properties. PPARs belong to the superfamily of nuclear hormone receptors and function as ligand-activated transcription factors. These have emerged as crucial players in the pathogenesis of AD. This review presented the potential of PPARs and their agonists in treating neurodegenerative diseases like AD.

Virtual screening of acetylcholinesterase inhibitors through pharmacophore-based 3D-QSAR modeling, ADMET, molecular docking, and MD simulation studies.

Alzheimer's disease (AD) is a leading cause of dementia in elderly patients. The pathophysiology of AD includes various pathways, such as the degradation of acetylcholine, amyloid-beta deposition, neurofibrillary tangle formation, and neuroinflammation. Many studies showed that targeting acetylcholinesterase enzyme (AChE) to improve acetylcholine can be an effective option to treat AD. In the current work, we employed a 3D QSAR-based approach to generate a pharmacophore to screen a chemical library of compounds that may inhibit AChE. Data from experimental studies were collected and used for the generation of pharmacophores. More than 1 million compounds were screened, and further drug-like properties were determined via in-silico ADMET studies. Techniques like molecular docking and molecular dynamics simulation were performed to analyze the binding of novel AChE inhibitors. A novel AChE inhibitor ligand-1 was identified as best with a docking score of -13.560 kcal/mol with RMSD of 1.71 Å during a 100 ns MD run. Further biological studies can give an insight into the potential of ligand-1 as a therapeutic agent for AD. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00189-1.

Cellular Senescence and Senolytic Agents: Recent Updates on Their Role and Applications.

Cellular senescence, an eternal condition of cell cycle arrest due to cellular stressors, is a sign of aging. Senescent cells (SCs) build up in tissues as they age, impairing their ability to repair themselves by causing the cell cycle to seize in progenitor cells and producing proinflammatory and the senescence-associated secretory phenotype (SASP) or matrix-degrading molecules. SASP aids in the emergence of several age-related diseases. Genetic studies have shown that removing SCs can delay aging and prolong life. Senolytics are small molecules designed to treat numerous age-related disorders can selectively kill SCs. A detailed discussion on senolytics and their potential as therapeutics to treat neuro-disorder and slow down aging is described herein. Emerging natural products, such as quercetin, dasatinib, fisetin, piperlongumine, and curcumin, have recently been reported to be effective senolytic agents, and some structurally modified analogue of these have also been explored for better selectivity and efficacy in animal models. These showed significant potential in clinical studies and could be developed as senolytic drugs in the future.

Networkodynamic approach to perceive the key phytoconstituents of E. officinalis (Amla) as natural BACE1 inhibitors: an in-silico study.

Alzheimer's disease (AD) is a deteriorating neural disorder, and currently, available drugs are ineffective in its treatment. Emblica officinalis (Amla) is widely recognised in the Indian medicinal system for ameliorative effects in managing diabetes, hyperlipidaemia and neurological diseases. Thus, we aimed to identify the active phytoconstituents of E. officinalis and their role in inhibiting the potential targets for the possible treatment of AD. The network pharmacology approach, gene ontology, molecular docking and molecular dynamics simulation (MDS) studies were performed. A total of 36 bioactive components in E. officinalis, 95 predicted anti-AD targets, and 3398 AD-related targets were identified from different databases. The network analysis showed that BACE1, ABCB1 and AChE, CA2 are the most potential AD targets. Based on gene ontology and topology analysis results, BACE1 was a significant target related to AD pathways, and quercetin, kaempferol and myricetin showed the highest interaction with target genes. The molecular docking results found that rutin and quercetin displayed better binding affinities -7.5, -5.67 kcal/mol than the BACE1 bound internal ligand. Furthermore, MDS results suggested that quercetin and rutin could be potential inhibitors against BACE-1 protein and may have therapeutic effects in treating AD. Such promising results could be further helpful in new drug discovery against AD.Communicated by Ramaswamy H. Sarma.

Convenient One-Pot Synthesis of Kynurenic Acid Ethyl Ester and Exploration to Direct Synthesis of Neuroprotective Kynurenic Acid and Amide Derivatives.

Kynurenic acid (KYNA) is an endogenous molecule, which is a non-selective antagonist of ionotropic glutamate receptors and has been found to have neuroprotective activity. A supplement of KYNA may be applicable for the treatment of neurodegenerative disease, but it does not cross the blood-brain barrier due to its polar nature. Therefore, its different esters and amide derivatives were explored as a prodrug, which can cross blood-brain barrier and transform into KYNA in situ. However, many esters and amide derivatives of KYNA are synthesized via coupling reaction or multi-step synthesis using different organic or metallic catalysts. Herein, we developed a novel one-pot, catalyst-free, convenient synthesis of KYNA ethyl esters using aniline and diethyl acetylene dicarboxylate in DMF under heating. We also explored the synthesis of KYNA and KYNA amide derivative in a simple manner with overall good yields via hydrolysis and condensation, respectively.

Coumarin as a Privileged and Medicinally Important Scaffold in the Treatment of Tuberculosis.

Coumarin and its derivatives, which are abundant in nature, have a significant role in medicinal chemistry due to their ability to bind with different targets or receptors. In addition, these possess a wide range of biological activity. Thus coumarin-based scaffold has inspired even further research into coumarin and its substituted derivatives, allowing for the creation of a huge variety of structurally different substituted products. In recent, these were reported to have potent antitubercular activity. Tuberculosis (TB) is a serious deadly infectious bacterial disease caused by grampositive Mycobacterium tuberculosis. This review discusses various developments going on in the field of medicinal chemistry towards designing, synthesizing, and discovering coumarin-based antitubercular agents all across the globe.

An Insight into MptpB Inhibitors as a Key Strategy to Treat MDR and XDRTuberculosis.

Tuberculosis (TB) is a chronic, air-borne infectious disease caused by Mycobacterium tuberculosis (Mtb), which prominently affects the lungs and usually manifests in other organs. TB is preventable and curable but what makes it challenging is the emergence of resistance to the available treatment options. MDR-continued TB's expansion is one of the world's most pressing and difficult problems. Mtb revives via the reciprocity between Mycobacterium and host signalling pathways. Mtb secretes a virulence component called Mycobacterium tuberculosis protein tyrosine phosphatase (MptpB), which helps to survive against host macrophages. It indicates that targeting secreted virulence factors offers more benefits to circumvent the emergence of resistance. Many effective inhibitors of MptpA and MptpB have been discovered, providing a solid foundation for future research and development. Aside from possessing a structurally unique binding site in the Mtb enzyme, MptpB's minimal resemblance to other human phosphatases provides a broad platform for improving selectivity over host PTPs. We believe that addressing several parts of infection processes in the host and bacteria with combination therapy is the greatest way to reduce treatment burden and medication resistance. We have discussed the recent potent, selective, and efficacious MptpB inhibitors, such as natural and marine-based, isoxazole- linked carboxylic acid-based, oxamic acid-based, and lactone-based inhibitors, as potential strategies for treating TB.

Strategies for Treatment of Disease-Associated Dementia Beyond Alzheimer's Disease: An Update.

Memory, cognition, dementia, and neurodegeneration are complexly interlinked processes with various mechanistic pathways, leading to a range of clinical outcomes. They are strongly associated with pathological conditions like Alzheimer's disease, Parkinson's disease, schizophrenia, and stroke and are a growing concern for their timely diagnosis and management. Several cognitionenhancing interventions for management include non-pharmacological interventions like diet, exercise, and physical activity, while pharmacological interventions include medicinal agents, herbal agents, and nutritional supplements. This review critically analyzed and discussed the currently available agents under different drug development phases designed to target the molecular targets, including cholinergic receptor, glutamatergic system, GABAergic targets, glycine site, serotonergic targets, histamine receptors, etc. Understanding memory formation and pathways involved therein aids in opening the new gateways to treating cognitive disorders. However, clinical studies suggest that there is still a dearth of knowledge about the pathological mechanism involved in neurological conditions, making the dropouts of agents from the initial phases of the clinical trial. Hence, a better understanding of the disease biology, mode of drug action, and interlinked mechanistic pathways at a molecular level is required.

Polymeric micelles loaded with glyburide and vanillic acid: I. Formulation development, in-vitro characterization and bioavailability studies.

The co-formulation of glyburide (Gly) and vanillic acid (VA) as such in the form of nanomedicine has never been explored to treat metabolic diseases including type 2 diabetes mellitus. Both the drugs possess dissolution rate-limited oral bioavailability leading to poor therapeutic efficacy. Hence, co-loading these drugs into a nanocarrier could overcome their poor oral bioavailability related challenges. Owing to this objective, both drugs were co-loaded in amphiphilic polymeric micelles (APMs) and evaluated for their biopharmaceutical outcomes. The APMs were prepared using mPEG-b-PCL/CTAB as a copolymer-surfactant system via the liquid antisolvent precipitation (LAP) method. The design of these APMs were optimized using Box Behnken Design by taking various process/formulation based variables to achieve the desired micellar traits. The release of both the drugs from the optimized co-loaded APMs was compared in different media and displayed a remarkable sustained release profile owing to their hydrophobic interactions with the PCL core. The in vitro cytotoxicity study of co-loaded APMs on Caco-2 cells revealed 70 % cell viability in a concentration-dependent manner. The preventive effects of Gly and VA co-loaded in APMs on glucose uptake was studied in insulin-responsive human HepG2 cells treated with high glucose. The co-loading of both the drugs in optimized APMs exhibited synergistic glucose-lowering activity (p < 0.001) than raw drugs with low cytotoxicity on HepG2 cells within the test concentration. This could be attributed to an increase in the relative oral bioavailability of both the drugs in APMs i.e., 868 % for Gly and 87 % for VA respectively.

BACE1: A Key Regulator in Alzheimer's Disease Progression and Current Development of its Inhibitors.

BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disease with no specific disease-modifying treatment. ß-secretase (BACE1) is considered the potential and rationale target because it is involved in the rate-limiting step, which produces toxic Aß42 peptides that leads to deposits in the form of amyloid plaques extracellularly, resulting in AD. OBJECTIVE: This study aims to discuss the role and implications of BACE1 and its inhibitors in the management of AD. METHODS: We have searched and collected the relevant quality work from PubMed using the following keywords "BACE1", BACE2", "inhibitors", and "Alzheimer's disease". In addition, we included the work which discusses the role of BACE1 in AD and the recent work on its inhibitors. RESULTS: In this review, we have discussed the importance of BACE1 in regulating AD progression and the current development of BACE1 inhibitors. However, the development of a BACE1 inhibitor is very challenging due to the large active site of BACE1. Nevertheless, some of the BACE1 inhibitors have managed to enter advanced phases of clinical trials, such as MK-8931 (Verubecestat), E2609 (Elenbecestat), AZD3293 (Lanabecestat), and JNJ-54861911 (Atabecestat). This review also sheds light on the prospect of BACE1 inhibitors as the most effective therapeutic approach in delaying or preventing AD progression. CONCLUSION: BACE1 is involved in the progression of AD. The current ongoing or failed clinical trials may help understand the role of BACE1 inhibition in regulating the Aß load and cognitive status of AD patients.

Current Perspective of ATP Synthase Inhibitors in the Management of the Tuberculosis.

INTRODUCTION: Tuberculosis is a life-threatening disease, and the drugs discovered during the era of 1950 and 1970 are found to be inefficient due to emergent MDR and XDR-TB. Tuberculosis is difficult to treat due to the development of antibiotic resistance. ATP synthase consists of two units, F1 and F0 units. These are present in the cytoplasm and membrane of mitochondria, respectively. F1 unit comprises of a, b, and c subunit while F0 subunit has α, ß, γ, δ, ε subunits. Bedaquiline was the first approved ATP synthase inhibitor in 2012 by USFDA. METHODS: Recent literature from 2005-2020 were collected using Pubmed with the keywords ATP synthase inhibitor, bedaquiline derivatives, tuberculosis. The work describing detailed analyses of bedaquiline (BDQ) was included in the current work, and others were excluded. RESULTS: ATP production occurs via the ATP synthase enzyme, leading to the growth and multiplication of mycobacteria. BDQ inhibits the mycobacterium ATP synthase enzyme, a heteropolymeric complex consisting of two subunits, but it does not interfere with mammalian ATP synthase. Bedaquiline (BDQ) has become a drug of choice in treating MDR-TB and helps in reducing the treatment span. Recently observed triple mutation as wtLeu59A→mtVal59A; wtIle66A→mtMet66A and wtGlu61B→mtAsp61B of ATP synthase led to decrease BDQ binding affinity; thus, researchers are putting efforts for its newer derivative discovery. CONCLUSION: ATP synthase inhibitor could be an alternative approach for better treatment of tuberculosis. Herein we discussed the recent advancements in the development of newer analogues of BDQ with its future perspectives.

Ameliorative potential of Operculina turpethum against streptozotocin-induced diabetes in rats: biochemical and histopathological studies.

The study aimed to investigate the acute toxicity, antidiabetic potential (in-vitro and in-vivo) of the Operculina turpethum (L.) Silva Manso at fraction level. The plant was fractionated into different fractions, i.e., flavonoid fraction (OTFF), tannin fraction (OTTF), saponin fraction (OTSF). In-vitro alpha-amylase inhibition assay revealed that OTFF was found to be more potent than standard Acarbose. The plant fractions were evaluated by MTT assay at different concentrations ranging from 100 to 1000 µg/ml. All the fractions were further evaluated for their safety profile, and the biochemical, hematology and histopathology result exhibits that the OTFF fraction produces mild toxicity at organ level at a concentration of 2000 mg/kg in albino mice. The in-vivo antidiabetic study was carried out on Sprague-Dawley rats using high-fat diet (HFD) feeding streptozotocin (STZ) diabetic model, and the biochemical, histopathology research findings represent that OTFF at a concentration of 500 mg/kg, p.o. was found to be highly significant among all the fractions and found to be more potent than the standard Acarbose. LC-MS characterization of the bioactive fraction OTFF showed the presence of rutin with m/z 610.52 in 50.50% and Apigenin 7-O-6'' acetyl-glucoside with m/z 475.42 in 24.10%; from molecular docking study, it is predicted that the fraction primarily acts as an alpha-amylase inhibitor and PPAR gamma agonist. In conclusion, the plant's OTFF fraction acts as a potential therapeutic agent for Type II diabetes mellitus.

p53 regulated senescence mechanism and role of its modulators in age-related disorders.

Multiple co-morbidities are associated with age, and there is a need for the broad-spectrum drug to prevent multiple regimens that may cause an adverse effect in the geriatric population. Cellular senescence is a primary mechanism for ageing in various tissues. p53, a tumor suppressor protein, plays a significant role in forming DNA damage foci and post different stress responses. DNA damage foci can be transient or persistent that can progress to DNA-SCARS inducing senescence. p53 also plays a role in apoptosis and negative regulation of SASP. Few upstream targets like FOXO4, MDM2, MDM4, USP7 control the availability of p53 for apoptosis. Hence, the senolytic therapies, modulating p53 upstream targets, can be a good approach for preventing age-related disorders. This review discusses the insights on the role of p53 in the formation of DNA-SCARS, various upstream target proteins, and pathways involved in p53 regulation. Further, the review aimed to include recently discovered small molecules acting on these upstream targets, and those can be modified using medicinal chemistry approaches to give successful senotherapeutics.

Harnessing amphiphilic polymeric micelles for diagnostic and therapeutic applications: Breakthroughs and bottlenecks.

Amphiphilic block copolymers are widely utilized in the design of formulations owing to their unique physicochemical properties, flexible structures and functional chemistry. Amphiphilic polymeric micelles (APMs) formed from such copolymers have gained attention of the drug delivery scientists in past few decades for enhancing the bioavailability of lipophilic drugs, molecular targeting, sustained release, stimuli-responsive properties, enhanced therapeutic efficacy and reducing drug associated toxicity. Their properties including ease of surface modification, high surface area, small size, and enhanced permeation as well as retention (EPR) effect are mainly responsible for their utilization in the diagnosis and therapy of various diseases. However, some of the challenges associated with their use are premature drug release, low drug loading capacity, scale-up issues and their poor stability that need to be addressed for their wider clinical utility and commercialization. This review describes comprehensively their physicochemical properties, various methods of preparation, limitations followed by approaches employed for the development of optimized APMs, the impact of each preparation technique on the physicochemical properties of the resulting APMs as well as various biomedical applications of APMs. Based on the current scenario of their use in treatment and diagnosis of diseases, the directions in which future studies need to be carried out to explore their full potential are also discussed.

In vitro anthelmintic activity of Chenopodium album and in-silico prediction of mechanistic role on Eisenia foetida.

Helminths born diseases are related to pitiable management practices and improper control strategies. The medicinal plants contain various phytoconstituents that are liable for their anthelmintic activity. The aerial parts of the Chenopodium album were successively extracted with microwaves assisted extraction using petroleum ether, ethyl acetate, methanol, hydroalcoholic and aqueous solvents to get respective extracts (CAPE, CAEE, CAME, CAHE, and CAAE). All the extracts were analyzed for preliminary phytochemical screening for the identification of phytoconstituents. The anthelmintic activity was analyzed on Indian adult earthworms Eisenia foetida using piperazine citrate (PCT) as a standard drug. All the extracts (apart from CAAE) lead to paralysis and fatality of the earthworms. CAEE extract exhibits highly significant anthelmintic activity at a 10 mg/ml concentration by causing paralysis and fatality of earthworms and was more potent than PCT suspension. At a concentration of 10 mg/ml, paralysis and death time for CAEE was recorded as (10.08 ± 1.11) and (65.28 ± 2.09) respectively, while for standard piperazine citrate, it was recorded as (22.96 ± 1.12) and (65.09 ± 1.23). The CAEE exhibits two major compounds by LC-MS, i.e., NG and DG, that are mainly accountable for the Chenopodium album anthelmintic activity. The plant possesses GABA-mimetic action and thereby leads to flaccid, reversible paralysis of the body wall muscle.

A Review on Natural Products and Herbs Used in the Management of Diabetes.

AIM: We aimed to review the importance of the natural products and herbs used in the management of diabetes mellitus (DM) as medicinal agents. BACKGROUND: Naturally occuring phytoactive compounds and herbs are very important because they are found to be effective against several diseases. DM is a commonly occurring endocrinological disorder, with the incidences increased four times in the last 34 years. There are several oral hypoglycemic agents available in the market, which in the long term, may lead to a high risk of secondary failure rate. OBJECTIVES: This review focuses on natural products and herbs application for effective management of diabetic conditions, and natural products that can be utilized as alternative therapy. METHODS: We searched the various online databases (PubMed, Bentham, ScienceDirect) and scientific publications from the library using a qualitative systematic review. The criteria of the review were based on natural products and herbs application for possessing medicinal value against diabetes and the literature of previous thirty years has been searched. The inclusion criteria of materials were based on the quality and relevancy with our aim. RESULTS: We observed that owing to the potential of natural products and herbs, different research groups are searching for the potent natural antidiabetic agents with minimal side effects. Recent research showed that there is a decline in a number of new molecules that fail in clinical trials because of toxicity thus, natural products and herbs are considered as the alternative. Currently, some of the natural products and herbs like coixol, andrographolide, Tinospora cordifolia, polypeptide p, charantin, Annona squamosa, and Nigella are being explored for their potential to be used successfully for the management of type 2 diabetes. CONCLUSION: The significance of natural products and herbs in the anticipation of diabetes and allied complications are being described herein. We observed that a huge amount of work is being done to explore the natural products and herbs to manage the diabetes and this review gives the highlights of them.

Development of L-Lysine Amino Acid-Based Co-Crystal of Telmisartan Using Crystal Engineering Approach to Improve Solubility, Dissolution, and Micrometric Properties.

AIM: To develop a co-crytsal of Telmisartan for enhancing its solubility in water. BACKGROUND: Intermolecular interaction happens in crystal packing; it utilizes and helps to understand the design of new solid with their respective chemical and physical properties called crystal engineering. It is a blueprint of molecular solids with specific chemical and physical properties through an understanding and handling of intermolecular interaction for increasing the solubility, in case of poor water-soluble drugs. OBJECTIVES: The study was taken under consideration with an aim to generate and synthesize a cocrystal form of Telmisartan (TEL) with L-lysine to improve its water solubility, dissolution, and micrometric properties. METHODS: Using dry grinding technique, solvent evaporation and cooling crystallization, the results revealed a generation of co-crystals with enhanced solubility by liquid drop grinding method. Hence, this process was further explored to investigate various formulations and process parameters that could significantly affect the crystal solubility, dissolution, and micrometric properties. RESULTS: The solubility of TEL co-crystals was enhanced by L-lysine. Further, the optimized batch was subjected to its micrometric evaluation and physiochemical characterization like FT-IR, NMR, PXRD. The result of the micrometric evaluation showed better results as compared to standards. The dissolution studies also showed a better dissolution rate for TEL co-crystal tablets than TEL tablets formulation. CONCLUSION: Co-crystals of TEL with L-lysine showed better solubility and dissolution rate.

Fail-safe nano-formulation of prodrug of sulfapyridine: Preparation and evaluation for treatment of rheumatoid arthritis.

Aim of the present study was to give a second life to the long-abandoned drug, sulfapyridine (SP) for its anti-arthritic potential by design of nano-vesicular delivery system. For this, intra-articular delivery of its liposomal formulation was tried. As the prepared formulation exhibited rapid drug leakage, an arthritis responsive prodrug of SP showing lability towards synovial enzymes was synthesized to exploit the over-expression of arthritis specific enzymes. Prodrug (SP-PD) exhibited better retention in liposomes as compared to the drug, preventing its escape from synovium. Hydrolysis of SP-PD in human plasma and synovial fluid indicated its high susceptibility to enzymes. The liposomes of SP-PD exhibited larger mean size, less PDI and higher zeta potential as compared to those for SP liposomes. In arthritic rats, prodrug liposomes were found to reverse the symptoms of inflammation, including the levels of biochemical markers. Liposomes of bio-responsive prodrug, therefore, offer a revolutionary approach in the treatment of rheumatoid arthritis.

Synthesis and evaluation of new 1,2,4-oxadiazole based trans- acrylic acid derivatives as potential PPAR-alpha/gamma dual agonist.

Diabetes is a ubiquitously a metabolic disorder and life-threatening disease. Peroxisome proliferator-activated receptors (PPARs) belong to the class of nuclear receptors which acts as transcription factors to regulate lipid and glucose metabolism. PPAR alpha/gamma dual agonists tend to corroborate the functions of both thiazolidinediones and fibrates and they hold substantial promise for ameliorating the type 2 diabetic treatments and providing potential therapeutic diabetic interventions. New 1,2,4-oxadiazole based trans- acrylic acid derivatives compounds possessing aryl/methylene linker in between pharmacophore head and lipophilic tail for dual PPAR-alpha/gamma agonists are studied. AutoDock Vina used for potential PPAR alpha/gamma dual agonists and 6 compounds 9a, 9g, 9 m, 9n, 9o, and 9r were identified comparable to PPAR gamma agonist Pioglitazone on the basis of their affinity scores and further their in-silico toxicity and in-silico ADME properties. The selected compounds showed better-calculated lipophilicity (iLogP) was found to be 0.92 to 3.19. Compound 9n and 9a were found to be most potent on both PPAR alpha and gamma receptors with EC50 of 0.07 ± 0.0006 µM, 0.06 ± 0.0005 µM and 0.781 ± 0.008 µM, 3.29 µM ± 0.03 respectively as better to pioglitazone having EC50 of 32.38 ± 0.2 and 38.03 ± 0.13 for both receptors. The in-vivo evaluation found to reduce the plasma glucose level and total cholesterol level significantly in diabetic rats compared to pioglitazone at 5 mg/kg/day dose for 7 days of treatment. Thus, trans- acrylic acid derivatives can be further developed as oral therapeutic agents for diabetic interventions as PPAR alpha/gamma dual agonists.

Recent Developments in Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors as a Valuable Tool in the Treatment of Type 2 Diabetes Mellitus.

In today's world, metabolic disorders are much dominant, and among them, diabetes is causing the highest rate of mortality. There is no cure for diabetes, while treatment could be done either by insulin therapy or oral antidiabetic drug. Oral antidiabetic agents target pathogenic factors like receptors, enzymes, genes and proteins involved in diabetes progression. Among them, recently, sodium-glucose co-transporters (SGLTs) have been recognized for their potential to effectively treat Type 2 diabetes mellitus. SGLTs are classified as SGLT-1 and SGLT-2, and among them, SGLT-2 is a major transporter which is involved in glucose reabsorption. Therefore, targeting SGLTs by its inhibitors could be a better choice to control the blood glucose level. Canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, luseogliflozin, and tofogliflozin are known to be SGLT-2 inhibitors. Herein, we discussed the current and future aspects of the development and applications of SGLT-2 inhibitors.