Marine drugs as putative inhibitors against non-structural proteins of SARS-CoV-2: an in silico study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an unprecedented pandemic, threatening human health worldwide. The need to produce novel small-molecule inhibitors against the ongoing pandemic has resulted in the use of drugs such as chloroquine, azithromycin, dexamethasone, favipiravir, ribavirin, remdesivir and azithromycin. Moreover, the reports of the clinical trials of these drugs proved to produce detrimental effects on patients with side effects like nephrotoxicity, retinopathy, cardiotoxicity and cardiomyopathy. Recognizing the need for effective and non-harmful therapeutic candidates to combat COVID-19, we aimed to develop promising drugs against SARS-COV-2. DISCUSSION: In the current investigation, high-throughput virtual screening was performed using the Comprehensive Marine Natural Products Database against five non-structural proteins: Nsp3, Nsp5, Nsp12, Nsp13 and Nsp15. Furthermore, standard precision (SP) docking, extra precision (XP) docking, binding free energy calculation and absorption, distribution, metabolism, excretion and toxicity studies were performed using the SchrÓ§dinger suite. The top-ranked 5 hits obtained by computational studies exhibited to possess a greater binding affinity with the selected non-structural proteins. Amongst the five hits, CMNPD5804, CMNPD20924 and CMNPD1598 hits were utilized to design a novel molecule (D) that has the capability of interacting with all the key residues in the pocket of the selected non-structural proteins. Furthermore, 200 ns of molecular dynamics simulation studies provided insight into the binding modes of D within the catalytic pocket of selected proteins. CONCLUSION: Hence, it is concluded that compound D could be a promising inhibitor against these non-structural proteins. Nevertheless, there is still a need to conduct in vitro and in vivo studies to support our findings.

Therapeutic modalities of human ß defensin-2 with prospective significance in diabetic wound treatment.

BACKGROUND: Diabetic Wounds (DW) are a debilitating complication of diabetes. Although various therapeutic strategies are available for DW management, none of them meet all the fundamentals due to the multifaceted pathophysiology of DW. Given the ever-present threat of DW, novel improved therapeutic strategies and the fortification of DW research deserve better prioritization. PURPOSE: The current review aims to provide the detailed role of human ß defensin-2 (HBD-2) in skin wounds with a prospective significance in DW treatment. METHODS: This review was conducted through searches of relevant abstracts, research and review articles, and patents, in Scopus, Web of Science, PubMed, Google Scholar, and Clinical Trials databases of English language articles. RESULTS: HBD-2 is a critical innate immune-response protein that defends the human body from infections. Recent reports also support the role of HBD-2 in suppressing inflammation and promoting proliferation and angiogenesis. Based on the literature, its therapeutic administration has been proposed to maintain the equilibrium of systemic homeostasis in DW. CONCLUSION: It has been hypothesized that HBD-2 could be a crucial modulator for controlling chronic inflammation and size by promoting proliferation and angiogenesis, opening up new therapy options in DW.

Filamentous temperature sensitive mutant Z: a putative target to combat antibacterial resistance.

In the pre-antibiotic era, common bacterial infections accounted for high mortality and morbidity. Moreover, the discovery of penicillin in 1928 marked the beginning of an antibiotic revolution, and this antibiotic era witnessed the discovery of many novel antibiotics, a golden era. However, the misuse or overuse of these antibiotics, natural resistance that existed even before the antibiotics were discovered, genetic variations in bacteria, natural selection, and acquisition of resistance from one species to another consistently increased the resistance to the existing antibacterial targets. Antibacterial resistance (ABR) is now becoming an ever-increasing concern jeopardizing global health. Henceforth, there is an urgent unmet need to discover novel compounds to combat ABR, which act through untapped pathways/mechanisms. Filamentous Temperature Sensitive mutant Z (FtsZ) is one such unique target, a tubulin homolog involved in developing a cytoskeletal framework for the cytokinetic ring. Additionally, its pivotal role in bacterial cell division and the lack of homologous structural protein in mammals makes it a potential antibacterial target for developing novel molecules. Approximately 2176 X-crystal structures of FtsZ were available, which initiated the research efforts to develop novel antibacterial agents. The literature has reported several natural, semisynthetic, peptides, and synthetic molecules as FtsZ inhibitors. This review provides valuable insights into the basic crystal structure of FtsZ, its inhibitors, and their inhibitory activities. This review also describes the available in vitro detection and quantification methods of FtsZ-drug complexes and the various approaches for determining drugs targeting FtsZ polymerization.

Human beta defensin-2 loaded PLGA nanoparticles impregnated in collagen-chitosan composite scaffold for the management of diabetic wounds.

Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. The standard treatment of DW care fails to address the prerequisites of treating DW owing to its multifactorial pathophysiology. Henceforth, developing a single treatment strategy to handle all the loopholes may effectively manage DW. The objective of the current study was to formulate Human beta defensin-2 (HBD-2) loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticle impregnated in collagen/chitosan (COL-CS) composite scaffolds for the accelerated healing of DW. Upon investigation, the developed biodegradable crosslinked scaffold possesses low matrix degradation, optimum porosity, and sustained drug release than the non-crosslinked scaffold. In vitro studies revealed that the HBD-2 COL-CS scaffold was biocompatible and accelerated cell migration and angiogenesis. The HBD-2 COL-CS scaffold showed significant antimicrobial activity in S. aureus, E. coli, and P. aeruginosa. The in vivo studies revealed that the HBD-2 COL-CS treated group accelerated healing compared to those in COL-CS and control groups. The ELISA results indicated a significant decrease in MMP-9, TNF-α, MPO, NAG, and NO with an increase in IL-10 in HBD-2 COL-CS treated group. The accelerated healing in HBD-2 COL-CS treated group might be due to the synergistic effects of PLGA (collagen synthesis and deposition and positive angiogenic effect), HBD-2 (anti-inflammatory, antibacterial, positive angiogenic effect, cell proliferation, and migration), COL (established wound healer and stabilizer) and CS (antibacterial, controlled drug release).

Synthetic Imidazopyridine-Based Derivatives as Potential Inhibitors against Multi-Drug Resistant Bacterial Infections: A Review.

Fused pyridines are reported to display various pharmacological activities, such as antipyretic, analgesic, antiprotozoal, antibacterial, antitumor, antifungal, anti-inflammatory, and antiapoptotic. They are widely used in the field of medicinal chemistry. Imidazopyridines (IZPs) are crucial classes of fused heterocycles that are expansively reported on in the literature. Evidence suggests that IZPs, as fused scaffolds, possess more diverse profiles than individual imidazole and pyridine moieties. Bacterial infections and antibacterial resistance are ever-growing risks in the 21st century. Only one IZP, i.e., rifaximin, is available on the market as an antibiotic. In this review, the authors highlight strategies for preparing other IZPs. A particular focus is on the antibacterial profile and structure-activity relationship (SAR) of various synthesized IZP derivatives. This research provides a foundation for the tuning of available compounds to create novel, potent antibacterial agents with fewer side effects.

Dual Acting Immuno-Antibiotics: Computational Investigation on Antibacterial Efficacy of Immune Boosters Against Isoprenoid H Enzyme.

Drug-resistant infections have become a serious threat to human health in the past two decades. Global Antimicrobial Surveillance (GLASS) in January 2018 reported widespread antibiotic resistance among 1.5 million people infected with bacteria across 22 countries. According to prominent economist Jim O'Neil, antimicrobial resistance is estimated to kill ∼10 million people affected by microorganisms each year by 2050. Even though multiple therapeutics are now available to treat the infections, more and more bacterial strains have acquired resistance to these treatments through various techniques. Moreover, the decrease in the pipeline of antibacterial medicines under clinical development has become a significant problem. In this scenario, the development of novel antibiotics that act on untapped pathways is necessary to combat the bacterial infections. Isoprenoid H (IspH) synthetase has become an attractive antibacterial target as there is no human homologue. IspH is an enzyme involved in methyl-d-erythritol phosphate (MEP) pathway of isoprenoid synthesis and is conserved in gram-negative bacteria, mycobacteria, and apicomplexans. Since, IspH is a novel therapeutic target, explorations are only just beginning, and despite the progress made in this area, no single IspH inhibitor is available in the market for therapeutic use. In this article, we have repurposed 35 immune boosters against IspH enzyme using methods such as extra-precision docking and Molecular Mechanics Generalized Born Surface Area (MMGBSA). Among them, 4'-fluorouridine was found to be active because of its glide score and significant binding affinity with IspH enzyme. Furthermore, this study requires more in vitro, in vivo, and molecular dynamics studies to support our findings.

Identification of novel protein kinase C-ßII inhibitors: virtual screening, molecular docking and molecular dynamics simulation studies.

Diabetic wounds (DWs) are the major end-stage manifestation encountered in diabetic patients. The two major pathways involved in the pathogenesis of DW are impaired angiogenesis and unnecessary NETosis, which are regulated by a common enzyme called protein kinase C (PKC)-ßII. PKC-ßII is a conventional isoform of PKC family that can be activated by calcium and diacylglycerol. PKC-ßII possesses a specific expression profile and plays a distinct role in various cellular and molecular functions. The pathogenic role of PKC-ßII and its involvement in the impairment of wound healing suggested that PKC-ßII plays a potential role in DW progression. Hence, there is a renewed interest in developing specific inhibitors of PKC-ßII. In the present study, receptor-based virtual screening was performed for the identification of potential PKC-ßII inhibitors using TimTec, Enamine, Zinc and Specs databases. A total of 595 candidate compounds were evaluated based on absorption, distribution, metabolism, excretion and toxicity, standard precision docking. Further, extra-precision docking and binding free energy calculations were carried out for top-ranked compounds. Based on Glide score and protein-ligand interactions, we have identified compound 1 as a potential inhibitor. Finally, molecular dynamics (MD) simulation was performed for top compound 1 using the Desmond module (Schrödinger suite) to identify the structural stability of the protein-ligand complex. Gratifyingly, MD trajectory analysis demonstrated the stable binding conformation of compound 1 with PKC-ßII enzyme. In silico approaches incorporated in this study provide a set of new putative PKC-ßII inhibitors which could be potential leads to develop DW therapeutics.

Imidazoles and benzimidazoles as putative inhibitors of SARS-CoV-2 B.1.1.7 (Alpha) and P.1 (Gamma) variant spike glycoproteins: A computational approach.

COVID-19 is an unprecedented pandemic threatening global health, and variants were discovered rapidly after the pandemic. The two variants, namely the SARS-CoV-2 B.1.1.7 (Alpha) and P.1 (Gamma), were formed by the mutations in the receptor binding domain of spike glycoprotein (SGP). These two variants are known to possess a high binding affinity with the angiotensin-converting enzyme 2. Amidst the rapid spread of these mutant strains, research and development of novel molecules become tedious and labour-intensive. Imidazole and benzimidazole scaffolds were selected in this study based on their unique structural features and electron-rich environment, resulting in increased affinity against a variety of therapeutic targets. In the current study, imidazole- and benzimidazole-based anti-parasitic drugs are repurposed against SARS-CoV-2 Alpha and Gamma variant spike glycoproteins using computational strategies. Out of the screened 15 molecules, flubendazole and mebendazole have exhibited promising binding features to the two receptors (PDB ID: 7NEH and 7NXC), as evidenced by their glide score and binding free energy. The results are compared with that of the two standard drugs, remdesivir and hydroxychloroquine. Flubendazole and mebendazole have become convenient treatment options against mutant lineages of SARS-CoV-2. The edge of the flubendazole was further established by its stability in MD simulation conducted for 100 ns employing GROMACS software. Further, in vitro and in vivo studies are essential to understand, if flubendazole and mebendazole indeed hold the promise to manage SARS-CoV-2 mutant stains. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11696-021-01900-8.

DFT calculation, molecular docking, and molecular dynamics simulation study on substituted phenylacetamide and benzohydrazide derivatives.

The atomic and molecular properties of the title compounds were calculated by Jaguar using a basis set B3LYP/6-31G**++ with hybrid DFT in the gas phase, to determine the chemical reactivity. Analysis of quantum chemical features such as HOMO and LUMO explained that the electronic charge transfer occurred within the system through conjugated paths of the selected compounds. The nucleophilic and electrophilic reactive sites are recognized from the molecular electrostatic potential plot. Electrophilic and nucleophilic attack-prone molecular sites were predicted by mapping ALIE value to the molecular surface. The bond dissociation energy of the high active compound 15 (2-chloro-N-(2-(2-(2-(2-chlorobenzoyl)hydrazineyl)-2-oxoethoxy)phenyl)acetamide) was calculated to assess the probability of compound autoxidation or degradation. Further, molecular docking, binding free energy calculations, and ADMET profile of the degradation products (DPs) of compound 15 was carried out to determine the binding affinity and toxicity profile of the formed DPs compared with the parent compound. A 150-ns molecular dynamics (MD) simulation was performed to evaluate the binding stability of the compound 15/4URL complex using Desmond. Binding free energy and binding affinity of the complex were computed for 100 trajectory frames using the MM-GBSA approach.

Preclinical models of diabetic wound healing: A critical review.

The treatment of diabetic wounds (DWs) is always challenging for the medical community because of its multifaceted pathophysiology. Due to practical and ethical considerations, direct studies of therapeutic interventions on human subjects are limited. Thus, it is ideal for performing studies on animals having less genetic and biological variability. An ideal DW model should progress toward reproducibility, quantifiable interpretation, therapeutic significance, and effective translation into clinical use. In the last couple of decades, various animal models were developed to examine the complex cellular and biochemical process of skin restoration in DW healing. Also, these models were used to assess the potency of developed active pharmaceutical ingredients and formulations. However, many animal models lack studying mechanisms that can appropriately restate human DW, stay a huge translational challenge. This review discusses the available animal models with their significance in DW experiments and their limitations, focusing on levels of proof of effectiveness in selecting appropriate models to restate the human DW to improve clinical outcomes. Although numerous newer entities and combinatory formulations are very well appreciated preclinically for DW management, they fail in clinical trials, which may be due to improper selection of the appropriate model. The major future challenge could be developing a model that resembles the human DW environment, can potentiate translational research in DW care.

Benzohydrazide and Phenylacetamide Scaffolds: New Putative ParE Inhibitors.

Antibacterial resistance (ABR) is a major life-threatening problem worldwide. Rampant dissemination of ABR always exemplified the need for the discovery of novel compounds. However, to circumvent the disease, a molecular target is required, which will lead to the death of the bacteria when acted upon by a compound. One group of enzymes that have proved to be an effective target for druggable candidates is bacterial DNA topoisomerases (DNA gyrase and ParE). In our present work, phenylacetamide and benzohydrazides derivatives were screened for their antibacterial activity against a selected panel of pathogens. The tested compounds displayed significant antibacterial activity with MIC values ranging from 0.64 to 5.65 µg/mL. Amongst 29 title compounds, compounds 5 and 21 exhibited more potent and selective inhibitory activity against Escherichia coli with MIC values at 0.64 and 0.67 µg/mL, respectively, and MBC at onefold MIC. Furthermore, compounds exhibited a post-antibiotic effect of 2 h at 1× MIC in comparison to ciprofloxacin and gentamicin. These compounds also demonstrated the concentration-dependent bactericidal activity against E. coli and synergized with FDA-approved drugs. The compounds are screened for their enzyme inhibitory activity against E. coli ParE, whose IC50 values range from 0.27 to 2.80 µg/mL. Gratifyingly, compounds, namely 8 and 25 belonging to the phenylacetamide series, were found to inhibit ParE enzyme with IC50 values of 0.27 and 0.28 µg/mL, respectively. In addition, compounds were benign to Vero cells and displayed a promising selectivity index (169.0629-951.7240). Moreover, compounds 1, 7, 8, 21, 24, and 25 (IC50: <1 and Selectivity index: >200) exhibited potent activity in reducing the E. coli biofilm in comparison with ciprofloxacin, erythromycin, and ampicillin. These astonishing results suggest the potential utilization of phenylacetamide and benzohydrazides derivatives as promising ParE inhibitors for treating bacterial infections.

Synthesis, Molecular Docking and Biological Evaluation of 2-Aryloxy-N-Phenylacetamide and N'-(2-Aryloxyoxyacetyl) Benzohydrazide Derivatives as Potential Antibacterial Agents.

A new class of 2-aryloxy-N-phenylacetamide and N'-(2-aryloxyoxyacetyl) benzohydrazide derivatives with different active moieties were synthesized and screened for their antibacterial activity. Structural characterization of synthesized compounds was performed using HR-MS, 1 H-NMR, and 13 C-NMR spectral data. Amongst the synthesized compounds, 4-{2-[2-(2-chloroacetamido)phenoxy]acetamido}-3-nitrobenzoic acid (3h) and 2-chloro-N-(2-{2-[2-(2-chlorobenzoyl)hydrazinyl]-2-oxoethoxy}phenyl)acetamide (3o) have shown good antibacterial activity against a selected panel of bacteria. Besides, compounds also exhibited bactericidal activity against P. aeruginosa (3h, 0.69 µg/mL) and S. aureus (3o, 0.62 µg/mL) as evident by MBC and time-kill kinetics studies. In silico molecular docking and ADMET properties of newly synthesized compounds revealed that compounds could be considered as promising antibacterial agents.

Ligand-based pharmacophore modeling and molecular dynamic simulation approaches to identify putative MMP-9 inhibitors.

MMP-9 is a calcium-dependent zinc endopeptidase that plays a crucial role in various diseases and is a ubiquitous target for many classes of drugs. The availability of MMP-9 crystal structure in combination with aryl sulfonamide anthranilate hydroxamate inhibitor facilitates to accentuate the computer-aided screening of MMP-9 inhibitors with the presumed binding mode. In the current study, ligand-based pharmacophore modeling and 3D-QSAR analysis were performed using 67 reported MMP-9 inhibitors possessing pIC50 in the range of 5.221 to 9.000. The established five-point hypothesis model DDHRR_1 was statistically validated using various parameters R 2 (0.9076), Q 2 (0.8170), and F value (83.5) at a partial least square of four. Hypothesis validation and enrichment analysis were performed for the generated hypothesis. Further, Y-scrambling and Xternal validation using mean-absolute error-based criteria were performed to evaluate the reliability of the model. Docking in the XP mode and binding free energy was calculated for 67 selected ligands to explore the key binding interactions and binding affinity against the MMP-9 enzyme. Additionally, high-throughput virtual screening was carried out for 2.3 million chemical molecules to explore the potential virtual hits, and their predicted activity was calculated. Thus, the results obtained aid in developing novel MMP-9 inhibitors with significant activity and binding affinity.

Synthesis and Preclinical Evaluation of Indole Triazole Conjugates as Microtubule Targeting Agents that are Effective against MCF-7 Breast Cancer Cell Lines.

CDATA[Background: Microtubules are considered to be an important therapeutic target for most of the anticancer drugs. These are highly dynamic structures comprising of α-tubulin and ß-tubulin which are usually heterodimers and found to be involved in cell movement, intracellular trafficking, and mitosis inhibition of which might kill the tumour cells or inhibit the abnormal proliferation of cells. Most of the tubulin polymerization inhibitors, such as Vinca alkaloids, consist of Indole as the main scaffold. The literature also suggests using triazole moiety in the chemical entities, potentiating the inhibitory activity against cell proliferation. So, in our study, we used indole triazole scaffolds to synthesize the derivatives against tubulin polymerization. OBJECTIVE: The main objective of this study to synthesize indole triazole conjugates by using environmentally friendly solvents (green chemistry) and click chemistry. To carry out the MTT assay and tubulin polymerization assay for the synthesized indole triazole conjugates. METHODS: All the synthesized molecules were subjected to molecular docking studies using Schrodinger suite and the structural confirmation was performed by Mass, proton-NMR and carbon-NMR, documented in DMSO and CDCL3. Biological studies were performed using DU145 (prostate cancer), A-549 (lung cancer) and, MCF-7 (breast cancer), cell lines obtained from ATCC were maintained as a continuous culture. MTT assay was performed for the analogues using standard protocol. Cell cycle analysis was carried out using flow cytometry. RESULTS: The Indole triazole scaffolds were synthesized using the principles of Green chemistry. The triazole formation is mainly achieved by using the Click chemistry approach. Structural elucidation of synthesized compounds was performed using Mass spectroscopy (HR-MS), Proton-Nuclear Magnetic Spectroscopy (1H-NMR) and Carbon-Nuclear Magnetic Spectroscopy (13C-NMR). The XP-docked poses and free energy binding calculations revealed that 2c and 2g molecules exhibited the highest docking affinity against the tubulin-colchicine domain (PDB:1SA0). In vitro cytotoxic assessment revealed that 2c and 2g displayed promising cytotoxicity in MTT assay (with CTC50 values 3.52µM and 2.37µM) which are in good agreement with the computational results. 2c and 2g also arrested 63 and 66% of cells in the G2/M phase, respectively, in comparison to control cells (10%) and tubulin polymerization inhibition assay revealed that 2c and 2g exhibited significant inhibition of tubulin polymerization with IC50 values of 2.31µM, and 2.62µM, respectively in comparison to Nocodazole, a positive control, resulted in an IC50 value of 2.51µM. CONCLUSION: Indole triazole hybrids were synthesized using click chemistry, and docking studies were carried out using Schrodinger for the designed molecules. Process Optimization has been done for both the schemes. Twelve compounds (2a-2l) have been successfully synthesized and analytical evaluation was performed using NMR and HR-MS. In vitro evaluation was for the synthesized molecules to check tubulin polymerization inhibition for antiproliferative action. Among the synthesized compounds, 2c and 2g have potent anticancer activities by inhibiting tubulin polymerization.

HER2 targeted biological macromolecule modified liposomes for improved efficacy of capecitabine in breast cancer.

The present research reports the beneficial effects of surface modified chitosan and tumor-homing peptide conjugated liposomes of capecitabine (CAP) for treating breast cancer. Liposomal formulation of CAP was prepared by film hydration method using cholesterol-THP conjugate (CTHP-CAP-LPs) to achieve active targeting through HER2 receptors. CTHP-CAP-LPs significantly improved the specificity and efficacy of CAP by improving cell uptake, cytotoxicity and tumor regression in tumor bearing mice. CTHP-CAP-LPs, therefore, is a promising approach to improve the anticancer effects of CAP.

Human beta defensins may be a multifactorial modulator in the management of diabetic wound.

Diabetic wound (DW) is considered as one of the serious complications associated with diabetes mellitus. Though some pharmacological approaches are available for managing DW, none of them has been reported to be very effective. Widely accepted options for its management include treatment of infection caused by various pathogens, wound debridement, reducing the period of the prolonged inflammatory phase, and supervision of the remodeling phase of wound healing. Satisfactory management of DW thus requires exploring new avenues for finding a potential therapeutic strategy. Literature shows that human beta defensins (HBDs) help in combating the insulin resistance by inhibiting the production of glucocorticoids, reducing chronic inflammation by acting through Toll-like receptor signaling pathway, and provoking cell migration, proliferation, angiogenesis, and stabilization of fibroblasts and keratinocytes, ultimately resulting in wound closure. In the present review, beneficial role of HBDs in the treatment of DW is discussed in detail.

Possible role of rivoglitazone thiazolidine class of drug as dual-target therapeutic agent for bacterial infections: An in silico study.

Infections due to resistant bacteria are the life-threatening and leading cause of mortality worldwide. The current therapy for bacterial infections includes treatment with various drugs and antibiotics. The misuse and over usage of these antibiotics leads to bacterial resistance. There are several mechanisms by which bacteria exhibit resistance to some antibiotics. These include drug inactivation or modification, elimination of antibiotics through efflux pumps, drug target alteration, and modification of metabolic pathway. However, it is difficult to treat infections caused by resistant bacteria by conventional existing therapy. In the present study binding affinities of some glitazones against ParE and MurE bacterial enzymes are investigated by in silico methods. As evident by extra-precision docking and binding free energy calculation (MM-GBSA) results, rivoglitazone exhibited higher binding affinity against both ParE and MurE enzymes compared to all other selected compounds. Further molecular dynamic (MD) simulations were performed to validate the stability of rivoglitazone/4MOT and rivoglitazone/4C13 complexes and to get insight into the binding mode of inhibitor. Thus, we hypothesize that structural modifications of the rivoglitazone scaffold can be useful for the development of an effective antibacterial agent.

Tumor homing peptide modified liposomes of capecitabine for improved apoptotic activity and HER2 targeted therapy in breast cancer: in vitro studies.

In the present study, we have formulated a liposomal formulation of cytotoxic agent capecitabine (CAP) to overcome its bioavailability issues. Then we have surface modified CAP loaded liposomes (CAP-LPs) with a tumour homing peptide (THP-CAP-LPs) to achieve site specific delivery to breast cancer cells. We found a significant cellular internalization of THP-CAP-LPs when compared to unmodified CAP-LPs. The cytotoxic effect of CAP was also significantly improved with THP-CAP-LPs by downregulating anti-apoptotic proteins and upregulating pro-apoptotic proteins as observed by Western blot analysis. THP-CAP-LPs mediated delivery of CAP can be, therefore, a promising approach for improving antitumor activity and reducing off-target effects.