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A series of new substituted benzimidazole-thiazoles (9a–l) have been designed and synthesized using 2-aminothiazole as a starting material by using molecular hybridization approach. The newly synthesized compounds were characterized by 1H NMR, 13C NMR and HRMS analyses. The compounds (9a–l) were evaluated for their in vitro antitubercular activity against Mtb (MTCC 300) strain. Among the screened compounds 9a, 9b, 9c and 9d have displayed promising antitubercular activity with MIC 7.55, 4.60, 15.39 and 28.38 μg/mL, respectively. All the compounds were further evaluated for their DPPH radical scavenging activity. The compounds 9a, 9b and 9d were exhibited excellent radical scavenging activity. In addition to this, single crystal structure of compound 9a was also studied. Furthermore, the high potency of these molecules was supported by ADME properties prediction as well as molecular docking study to gain an insight into the binding mode and affinity toward mycobacterial InhA.

Breast cancer is one of the most prevalent cancers in women and a leading cause of mortality. As per the GLOBCAN report of 2021, breast cancer has surpassed lung cancer which until recently was the most commonly diagnosed cancer. Despite significant efforts to improve early detection and therapeutic efficacy of breast cancer, the frequent emergence of drug resistance remains the predominant basis for the poor prognosis of cancer patients harboring various malignancies. Long non-coding RNA (lncRNAs) are known to affect a variety of components of genome function, including epigenetics, gene transcription, splicing, translation, as well as many central biological processes like cell cycle progression, cell differentiation, development, and pluripotency. LncRNAs are dysregulated in various malignancies and interact with a multitude of RNAs and proteins to impact drug resistance. LncRNAs regulate chemoresistance in cancer by employing an assortment of molecular mechanisms including multidrug efflux, suppression of apoptosis, DNA damage response, epigenetic alterations, as well as functioning as competitive endogenous RNA. When combined with other regulatory mechanisms, these pathways form a complex orchestration of signaling that ultimately lead to chemoresistance. The current review delves into the role of lncRNAs in inducing drug resistance to conventional therapeutic anti-cancer drugs used for the treatment of breast cancer. We propose that lncRNAs that provoke drug resistance could be used to develop new targeted and tailored therapeutics providing a novel approach to introduce promising personalized treatment modalities to overcome chemoresistance in breast cancer patients. Hence, lncRNAs that drive anticancer drug resistance can be potentially explored as biomarkers of disease prognosis and may provide unique opportunities to circumvent chemoresistance in breast cancer patients.

The antioxidant potential (% RSA and EC50) of solvent extracts of leaves and roots of Lobelia nicotianifolia Roth. was assessed using five in vitro assays. The EC50 values of methanolic extract wer...

Objective: The study aims at the derivatization of “Phthalides” and synthesizes 3- arylaminophthalides & 3-indolyl-phthalides compounds, and evaluates their anti-tubercular and antioxidant activities. The study has also intended to employ the in silico methods for the identification of possible drug targets in Mycobacterium and evaluate the binding affinities of synthesized compounds. Methods: This report briefly explains the synthesis of phthalide derivatives using ammonium chloride. The synthesized compounds were characterized using spectral analysis. Resazurin Microtiter Assay (REMA) plate method was used to demonstrate the anti-mycobacterial activity of the synthesized compounds. An in-silico pharmacophore probing approach was used for target identification in Mycobacterium. The structural level interaction between the identified putative drug target and synthesized phthalides was studied using Lamarckian genetic algorithm-based software. Results and Discussion: In the present study, we report an effective, environmentally benign scheme for the synthesis of phthalide derivatives. Compounds 5c and 5d from the current series appear to possess good anti-mycobacterial activity. dCTP: deaminasedUTPase was identified as a putative drug target in Mycobacterium. The docking results clearly showed the interactive involvement of conserved residues of dCTP with the synthesized phthalide compounds. Conclusion: On the eve of evolving anti-TB drug resistance, the data on anti-tubercular and allied activities of the compounds in the present study demonstrates the enormous significance of these newly synthesized derivatives as possible candidate leads in the development of novel anti-tubercular agents. The docking results from the current report provide a structural rationale for the promising anti-tubercular activity demonstrated by 3-arylaminophthalides and 3-indolyl-phthalides compounds.

Leishmaniasis is one of the most neglected tropical diseases that demand immediate attention to the identification of new drug targets and effective drug candidates. The present study demonstrates the possibility of using threonine synthase (TS) as a putative drug target in leishmaniasis disease management. We report the construction of an effective homology model of the enzyme that appears to be structurally as well as functionally well conserved. The 200 nanosecond molecular dynamics data on TS with and without pyridoxal phosphate (PLP) shed light on mechanistic details of PLP-induced conformational changes. Moreover, we address some important structural and dynamic interactions in the PLP binding region of TS that are in good agreement with previously speculated crystallographic estimations. Additionally, after screening more than 44,000 compounds, we propose 10 putative inhibitor candidates for TS based on virtual screening data and refined Molecular Mechanics Generalized Born Surface Area calculations. We expect that structural and functional dynamics data disclosed in this study will help initiate experimental endeavors toward establishing TS as an effective antileishmanial drug target.

Natural products with targeted bioactivity have gained major attention in the field of cancer research owing to emerging anti-cancer drug resistance and off target toxicities. Chloroxylon swietenia (Roxb.) DC is recognized as a folklore medicinal plant and has numerous therapeutic benefits in the folklore medicine system, however the anti-cancer potential of this plant and its mechanism of action is poorly understood.The aim of the study was to investigate the anti-breast cancer efficacy of C. swietenia leaves methanol extract (CSLME) against MCF-7 hormone dependent human breast cancer cell line with possible mechanism of action.The anti-breast cancer activity of CSLME against MCF-7 cells was assessed by evaluating its efficacy toward cytotoxicity, cell migration, colony formation, DNA fragmentation, apoptosis, cytoskeleton, angiogenesis, cell cycle regulation, and animal toxicity. The preliminary screening of CSLME against MCF-7 cells revealed the cytotoxicity (ICThe in vitro and in vivo findings clearly outline the potential of CSLME as inhibitor of growth and proliferation of MCF-7 cells. Mechanistically, CSLME seems to activate intrinsic pathway of apoptosis, arrest cell cycle, target actin cytoskeleton, inhibit growth, colony formation, migration, and angiogenesis, with down regulation of NF-κB pathway leading to cell death.

The soybean peroxidase (SBP) mediated nanohybrid [SBP-Cu3(PO4)2·3H2O] synthesis was carried out in the present study. The scanning electron microscopy (SEM) analysis showed a characteristic flower-like hierarchical structure of the SBP-nanohybrid. The mechanism of SBP-nanohybrid formation was elucidated using computational approaches. The predicted Cu2+ binding sites followed by molecular docking studies showed the two lowest energy (−4.4 kcal/mol and −3.56 kcal/mol) Cu2+ binding sites. These two binding sites are located at the opposite position and might be involved in the formation of SBP-nanohybrid assemblies. Further, these sites are different than the catalytic active site pocket of SBP, and may facilitate more substrate catalysis. Obtained computational results were confirmed by in-vitro guaiacol oxidations studies using SBP-nanohybrid. The effect of various parameters on SBP-nanohybrid activity was studied. The pH 7.2 was found optimum for SBP-nanohybrid activity. The enzyme activity increased with an increase in temperature up to 50 °C temperature and then decreased with an increase in temperature. Around ∼138% enhanced activity was recorded using SBP-nanohybrid compared to crude SBP. Also, the SBP-nanohybrid showed around 95% decolorization of methylene blue (MB) in 1 h and the MB degradation was confirmed by high-pressure liquid chromatography analysis (HPLC). Communicated by Ramaswamy H. Sarma

A series of novel indazole derivatives has been synthesized and evaluated for anticancer, antiangiogenic, and antioxidant activities. The capability of the synthesized compounds 11a–x to hinder the viability of three human cancer cells lines, HEP3BPN 11 (liver), MDA 453 (breast), and HL 60 (leukemia), were assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Among the compounds 11a–x screened, 11c and 11d showed the higher inhibitory activity on the viability of HEP3BPN 11 (liver), when compared with the standard methotrexate. These compounds were further tested to evaluate their potential to inhibit the proangiogenic cytokines associated with tumor development. Compound 11c was found to be a potent antiangiogenic agent against TNFα, VEGF, and EGF, whereas 11d showed potent antiangiogenic activity against TNFα, VEGF, IGF1, TGFb, and leptin inhibition. All the compounds 11a–x were screened for their antioxidant activities using 2,2-diphenyl-1-picryl hydrazine (DPPH), hydroxyl (OH), and superoxide radical (SOR) scavenging activity. Compounds 11n, 11p, 11q, and 11v have shown significant OH radical scavenging activities, also compounds 11c, 11h, and 11k were found to have a DPPH radical scavenging activity and compounds 11a and 11m exhibited better SOR scavenging activity when compared with the reference compound ascorbic acid. In silico molecular docking analysis revealed important structural insights behind observed anti TNFα effect by present indazole compounds.

Introduction Historically, medicinal plants and natural products have been used to treat a variety of human health issues and there has been renewed interest in their use for integrated cancer management. The present investigation was aimed to evaluate the anti-breast cancer, anti-angiogenic and antioxidant potential of selected local botanicals. Methods The methanolic extracts of Cassia occidentalis, Callistemon viminalis, Cleome viscosa and Mimosa hamata were assessed for their cytotoxic properties against a human breast cancer cell line MCF-7 by using the Sulforhodamine B (SRB) assay. The anti-angiogenic potential of all plant extracts was assessed by using an in vivo chorioallantoic membrane (CAM) model. Furthermore, the antioxidant potential of plant samples was evaluated using 2, 2-diphenyl-1-picryl hydrazine (DPPH), hydroxyl (OH) and superoxide radical (SOR) scavenging assays. Results The results of the present investigation revealed that all the selected plant extracts: C. occidentalis (IC50 = 70 ± 0.11 μg/ml), C. viminalis (IC50 = 44 ± 0.19 μg/ml), C. viscosa leaves (IC50 = 70 ± 0.22 μg/ml), C. viscosa root (IC50 = 73.2 ± 0.36 μg/ml) and M. hamata (IC50 = 65.8 ± 0.25 μg/ml) demonstrated an effective cytotoxic effect against MCF-7 cells. In the CAM model, the plant extracts exhibited significant anti-angiogenic activity by inhibiting the blood vessels density. Amongst the tested samples, the most efficient anti-angiogenic effect was demonstrated by extract of C. viminalis (67.76 ± 0.77%). Additionally, all the studied plant extracts were found to possess considerable antioxidant activity. Conclusion The selected botanicals with their anti-angiogenic and antioxidant potential could be considered as natural resources in the identification of possible therapeutic agents for breast cancer.

Chemotherapy anticancer drugs and plant-based foods (mostly fruits, vegetables, whole grains, fruit juices and also derived beverages) have an intricate association with human health and cancer progression. The negative part of food–drug interactions is associated with alterations in the therapeutic effects of drug molecules by affecting their pharmacokinetic or pharmacodynamic properties leading to adverse clinical outcomes. This aspect is an important framework that needs to be considered because diet–drug interactions are likely to happen during the episodes of chemotherapy treatment. Taking into consideration the public health significance of the issue, the US Food and Drug Administration (fda.gov) has provided “Clinical Drug Interaction Studies-Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry”. The circumstantial literature describes that oral chemotherapy drugs and food interactions are associated with significant impact on the pharmacokinetics of orally administered anticancer agents, which adversely affect the bioavailability, absorption and other pharmacokinetic parameters and possibly limit the benefits of chemotherapy drugs. Several herbal products such as garlic, echinacea, ginseng, milk thistle, grapefruit juice and St John’s work have demonstrated interactions with variety of cancer chemotherapeutic drugs in humans. Therefore, in the midst of evolving targeted anticancer drug developments it is rational to revisit the complexities of food–drug interaction so as to aware the cancer patients towards this important but not frequently discussed issue.

Series of diet- and nutrition-related questions raised by cancer survivors are waiting to be addressed scientifically. Diet and nutritional recommendations and guidelines suggested by worldwide agencies are either inconsistent or lack the mechanistic and rigorous clinical evidence. Patient-oriented and cancer-specific dietary recommendations are limited. Moreover, the impact of dietary recommendations is not effective owing to moderate interest of clinical oncologists in diet and nutritional interventions. The evolving preclinical and clinical research suggests that the survival of cancer patients is closely associated with dietary interventions, pattern of diet, fasting, calorie restriction and role of dietary ingredients in the pathophysiology of cancer progression. The current landscape of dietary research shows that the diet and dietary ingredients interact with cancer cell proliferating signalling pathways, epigenetic factors, metastasis, cancer stem cells, tumour suppressor or oncogenic miRNAs, and anticancer drug targets. Although a sizable volume of research has been carried out in the diet–cancer area, however, still diet-mediated molecular mechanisms proving benefits to cancer patients are poorly understood and there lies an opportunity of unravelling the diet-mediated inscrutable molecular mechanisms. Some nonscientific illusions about the risk and benefits of dietary supplements (especially antioxidants and vitamins) prevailing in the minds of cancer patients still waiting to be addressed in the mechanistic framework along with launching evidence-based diet-related awareness programmes. Looking forward, the most upcoming discourse may be to investigate the dynamic interplay between dietary interventions and cancer microbiome. There is ample research opportunity to understand the cancer-specific role of human microbiome. Moreover, the future research opportunities in understanding the role of dietary intervention in improving cancer immunosurveillance may be useful in integrating these nonpharmacological regimens with cancer immune therapy.

In the current state of the art, there is widespread usage of dietary supplements (DSs) by cancer patients both during the cancer treatment and during the drug holidays as well. However, there is lack of empirical data in relation to their safety or efficacy. The available research data show that there should be judicious usage of DSs by cancer patients, which otherwise may aggravate the progression of cancer. Besides these ground clinical realities about the benefits of DSs in cancer prevention, the market of DSs is growing in logarithmic fashion. US people spent over $36 billion in 2014 on dietary supplements. In fact, the consumer victimizing advertisements of DSs are easily accessed by cancer survivors through Internet, social media and television and inspire them to use it as an adjunct or traditional therapy. These self-prescriptions of DSs by cancer patients are mostly based on anecdotal evidences. More often owing to the drastic change in the psychology and mindset of cancer patients, they do not inform the inclusions of DSs to oncologist or their primary caretakers. There is need to rationalize the intake of DSs and quantify the does by assessing the analytical profile of need and deficiency in individual cancer type/patient so as to avoid the DS-related adversities and minimize the financial burden.

The burden of cancer is increasing across the world and accounting for major cause of mortality. Chemotherapy, radiotherapy and surgical procedures are the current approaches for the management of cancer. The preclinical and clinical research suggests that antioxidants are effective in preventing oxidative stress, which is considered as a major culprit for initiation and progression of cancer. Therefore, antioxidants are advised as an adjuvant treatment modality during chemotherapy or radiotherapy treatment of cancer survivors. In the current state of the art, cancer survivors frequently consume the dietary and supplemental antioxidants for the prevention of cancer. Antioxidants are believed to interact with various targets of cancer and arrest cell growth, proliferation, migration, EMT and metastasis and also neutralize the free radicals or reactive oxygen/nitrogen species, which are involved in initiation and progression of cancer. Besides the great strides of advances made in understanding the molecular mechanism of cancer progression, still the concrete mechanisms demonstrating the benefits and adverse effects of antioxidants are poorly understood. However, there is mounting evidence accumulating in the literature, which reports that antioxidant molecules do not demonstrate absolute antitumour or anticancer properties. Nevertheless, few reports also pinpoint the involvement of antioxidants in initiation and progression of cancer. Considering the dynamics of current research outcomes, it seems that antioxidants possess contextual two-faced bioactivity towards cancer prevention and promotion as well. The design and conduct of double-blinded randomized clinical trials can be a gold standard for validating the preclinical anticancer claims of antioxidants and which perhaps will help in integrating the use of antioxidants in the management of cancer. Adequate clinical validation is essential to determine the efficacy of antioxidants or antioxidant supplements in combination with different anticancer agents. The research is evolving in this direction as it can be evidenced by registration (until June 2021) of over 41 clinical trials (ClinicalTrials.gov) out of which 50% are completed.

Epidemiological studies have clearly demonstrated the fact that diet and nutrition have profound impact and influence on the progression of cancer and also on risk of developing cancers. Besides great strides of efforts in dietary research, till today series of diet- and nutrition-related questions raised by cancer survivors are waiting to be addressed scientifically. Diet and nutritional recommendations and guidelines suggested by worldwide agencies are either inconsistent or lack the mechanistic and rigorous clinical evidence. Patient-oriented and cancer-specific dietary recommendations are limited. Moreover, the impact of dietary recommendations is not effective owing to moderate interest of clinical oncologists in diet and nutritional interventions. The evolving preclinical and clinical research suggests that the survival of cancer patients is closely associated with dietary interventions, pattern of diet, fasting, calorie restrictions and action of dietary ingredients with respect to the pathophysiology for cancer progression. Furthermore, the outcome of preclinical research has demonstrated that the prognosis of cancer could be altered by modifying or restricting diet. The emerging research in diet–cancer discourse includes the diet/metabolite-mediated regulation of cancer signalling pathways/growth factors, interaction with anticancer targets, metastasis, cancer stem cells, cancer-related miRNAs, drug–diet interaction, immunosurveillance, drug toxicity, side effects and cancer microbiome. The upcoming trends in the dietary research are coevolving with the advances in molecular aspects of cancer biology, and perhaps such research outcome may serve as a baseline reference for developing evidence-based guideline for various stakeholders in the mainstream of cancer management.

The ecosystem of cancer management is exploring the multiple approaches for the effective management of cancer. In the quest of integrated cancer management, the beneficial therapeutic effects of fasting/calorie restriction (CR) or fasting-mimicking diet (FMD) have inspired researchers and clinicians owing to their benefits to cancer patients towards overall survival, disease prevention, improvements in treatments and amelioration of side effects and off-target toxicities. There are growing preclinical clinical evidences, which describe the anticancer effects of fasting/CR or FMD by reducing cancer progression, inducing the mortality of cancer cells and improving the effectiveness and tolerability of chemo- and radiotherapies. Series of clinical trials are being launched and several completed (ClinicalTrials.gov) for addressing the interventions of fasting/CR or FMD in caner management; however, the overall outcome of studies seems to be inconsistent and perhaps focused randomized clinical trials are still required to understand their multidimensional molecular effects under different settings of cancer therapy. As a part of understanding the molecular basis of fasting/CR or FMD, the experimental data indicate that fasting/CR or FMDs significantly deplete the levels of tumour growth essential nutrients and factors, including glucose, IGF1 and insulin. Apart from significant decrease in the ratio of ATP/ADP and NADH/NAD, there is upregulation of variety of proteins, which are involved in apoptosis, autophagy, detoxification, DNA repair, genomic stability and immunosurveillance, while several proteins and pathways implicated in cell proliferation and oxidative damage are downregulated. Interestingly, fasting/CR or FMD may demonstrate altogether different and even opposite effects in different cancer cell types or even within the same cancer cell type.

A vast body of literature has accumulated in the past two decades, which is consistently reporting the significance of dietary bioactive metabolites as possible target-oriented anticancer agents. Diet origin substances like curcumin, sulforaphane, resveratrol, quercetin, epigallocatechin gallate and hundreds of dietary polyphenols have been extensively studied as anticancer agents in preclinical and clinical settings. Until now, over hundreds of different dietary molecules have been identified, which need to be translated into clinical practice so as to expand their clinical utility in medicine as an adjuvant therapy. Employing approaches like proteomics, transcriptomics, metabolomics and microbiomics might pave the way for understanding of how dietary factors interact with hallmarks of cancer drug targets and chemotherapy drugs and contribute in cancer prevention. Nevertheless, there is also an equal research opportunity to conduct research for improving the bioavailability of the effective anticancer dietary agents.

Functional foods comprise foods or food components that have potential to provide health benefits beyond basic requirements of nutrition. It is believed that functional foods are value-added products, which not only provide nutrients but also help to maintain good health and reduce the risk of diseases including cancer. “Nutraceuticals” is a combination of two words “nutrition” and “pharmaceutical”, which have demonstrated positive effects on overall health well-being, and also complements for prevention and treatment of diseases including cancer.

Cancer metastasis happens to be one of the key processes closely associated with morbidity and mortality of cancer patients. Majority of the currently used chemotherapy drugs are targeted towards primary cancer cells and the agents targeting the process of metastasis are not available and the research is evolving in this direction. A variety of dietary agents have been recently described to act as inhibitors of metastasis at various stages of its development. In the preclinical settings, variety of diet origin bioactive molecules have been explored for their role in regulation of metastasis suppressor genes, variety of metastasis signalling molecules, enzymes (especially MMPs) involved in metastasis and key metastasis-related processes such as epithelial–mesenchymal transition (EMT), invasion and angiogenesis. The preclinical and clinical literature clearly advocates that appropriate dietary modification has potential to suppress the process of metastasis in cancer patients and thereby may improve their survival and quality of life. The search of antimetastatic agents from dietary sources not only help in integrated management of cancer prevention but will also inspire the development of novel chemotherapy agents targeting metastasis.

Approximately 50–85% of the human genome is transcribed, and only 1–3% of cellular transcription corresponds with protein-coding DNA sequences. The NGS showed that majority of the human transcriptome over 97–99% is composed of small noncoding RNAs (ncRNAs). MicroRNAs (miRNAs) are a class of ncRNAs that play an important function in regulating gene expression. The advancements in high-throughput functional analysis have unravelled the regulatory functions of variety of miRNAs, which includes the epigenetic regulators of cancer progression, proliferation, metastasis, cell differentiation and cancer stem cells, and also implicated in the regulation of epithelial-to-mesenchymal transition (EMT: a key factor for metastasis) of cancer cells. The therapeutic and pathophysiological roles of miRNAs have inspired the research community, which can be evidenced by citing registration (until June 2021) of 368 clinical trials (ClinicalTrials.gov) associated with various aspects of miRNAs in human ailments. Interestingly, over 132 clinical trials have been completed involving the intervention of “miRNAs” in human disease biology. Literature accumulated in the recent past demonstrated the role of dietary metabolites as downregulators of oncogenic miRNA and inducing the expressions of tumour suppressor miRNAs. Variety of commonly consumed foods like grapes, onions, garlic, cruciferous vegetables (mostly broccoli), soya bean, green tea, Mentha species, variety of citrus fruits, ginger, turmeric, cabbage, collards, cauliflower, kale and mustard greens have demonstrated the potential to inhibit the oncogenic miRNAs and activate the tumour suppressor miRNAs in variety of cancer under preclinical settings.

The plethora of preclinical research data inspired the scientific community and pharma sector to design and conduct the clinical trials for assessing the dietary interventions in cancer prevention, improvising the outcome of chemotherapy and reducing toxicity and many other aspects related to betterment of cancer patient’s life. Over 1000 clinical trials of diet, nutrition, dietary supplements and foods in relation to cancer are registered at clinicaltrials.gov. Unfortunately, none of the clinical effects of dietary interventions have been approved by FDA for cancer prevention. Therefore, the upcoming clinical research settings should be more focused on understanding the molecular mechanisms and mode of action of dietary interventions on tumour/cancer cell metabolism and its impact on current chemotherapy efficacy. Such endeavours may help to develop dietary modifications as adjuvant therapeutic approach for effective management of cancer.

Besides the great strides of efforts made towards understanding the effect of fasting, calorie restriction (CR) and fasting-mimicking diet (FMD), yet there is growing curiosity among the cancer survivors towards this unresolved question whether fasting/CR/FMD has any role to play in the progression and treatment of cancer. Few notable questions being asked by the cancer patients pertain to efficacy of fasting/CR/FMD in arresting the progression of cancer, killing of cancer cells, boosting of the immune system, and whether it has role in improving the effectiveness of currently prescribed chemotherapy and radiation therapy? The sensitivity of cancer cells towards nutrient depletion and their dependency on alternate metabolites has been emerged as a hallmark of cancer. The current preclinical and clinical research finding has demonstrated that fasting, calorie restriction or fasting-mimicking diets induce variety of alterations in growth factors, levels of metabolites, etc., which ultimately leads into creation of an environments that has potential to reduce the adaptive abilities of cancer cells towards survival and thereby helps in improving the efficacy of cancer chemotherapy. Moreover, fasting/calorie restriction or FMDs have been reported to increase resistance towards chemotherapy drugs in normal cells; however, it is not found in cancer cells and thereby promote regeneration effects in normal cells. These dramatic effects of fasting/FMD may help in preventing the detrimental side effects of chemotherapy drugs. Although fasting cannot be tolerated by patients, however, the current preclinical and clinical studies demonstrated feasibility and safety of periodic fasting or FMDs. Taking into considerations the current literature, it is possible to integrate the periodic fasting or FMDs with chemotherapy, cancer immunotherapy or other cancer treatments, which may increase the therapeutic index of cancer treatments and circumvent the emerging resistance and side effects or off-target toxicities.

The issue of providing dietary guidelines to cancer survivors is important owing to the influence of dietary factors in cancer patients undergoing treatment and also after drug holidays. Several National and International agencies, which are involved in cancer research and public health care, have taken lead in providing diet-related information and guidance for cancer survivors. Worldwide, series of clinical, preclinical and epidemiological reports are accumulating in logarithmic fashion linking the role of diet, dietary patterns, ingredients and nutrition with cancer survival and mortality. Moreover, the notable cancer-related worldwide national and international organizations are providing dietary and nutritional guidelines for the cancer patients. For example, World Cancer Research Fund International (WCRF: wcrf.org) in collaboration with American Institute for Cancer Research (AICR) is running a programme called continuous update project (CUP), wherein the worldwide experts are consistently analysing and interpreting the diet- and cancer-related scientific literature (clinical, epidemiological, cohort, observational and case studies) and providing the evidence-based recommendations in relation to diet, nutrition and physical activity in concert with cancer risk and survival of different types of cancer patients across the world. Although the present global profile dietary recommendation is consistently inconsistent, however, the ultimate aim of dietary research is to provide the patient-centric dietary information/guidelines, which at present is lacking to a greater extent.

The research in the past two decades identified the dietary patterns and bioactive ingredients, which helped to establish a baseline data for the formulation of cancer prevention guidelines and fuelled the area of developing dietary patterns with the aim of cancer prevention and improving the overall survival of cancer patients. Conventionally, a dietary pattern is described as “The quantity, variety, or combination of different foods and beverage in a diet and the frequency with which they are habitually consumed”. Among the dietary pattern’s variety, Mediterranean pattern (which comprises of olive oil, fruits, legumes, fish and vegetables), ketogenic dietary pattern (a high-fat intake, moderate protein and low-carbohydrate intake), vegan (abstains from all animal products) and vegetarian dietary pattern, alkaline dietary pattern and specific diet (deficient of one or more unique molecules) are some of the dietary patterns associated with cancer prevention. The preclinical and clinical data accumulated in the recent past advocate the benefits of different dietary patterns in relation to different cancers; however, there is little convincing evidence, which suggests that particular dietary pattern positively influences the outcomes in relation to prognosis, recurrence and mortality. The limited evidences exist, which describe the individual dietary patterns and their useful effects; however, overall, the Western dietary pattern seems to be detrimental for variety of cancers.

The researches in past one decade have identified cancer stem cells (CSCs) as a major culprit of recurrence, heterogeneity, metastasis, drug and radioresistance in cancer treatment. With the increasing awareness of the significance of a dietary intervention in human health, the research is also coevolving with the molecular understanding of association between diet and cancer. Cancer stem cells are a subpopulation of cancer cells with unique characteristics of self-renewal potential, aggressive invasiveness, promoting metastasis and demonstrated resistance against chemo- and radiotherapy. The preclinical data have clearly demonstrated the anticancer effects of dietary substances against CSCs. Series of dietary ingredients inhibit the CSC-associated signalling pathways and ultimately adversely affect maintenance of CSC stemness, survival and proliferation. To integrate the anti-CSCs dietary molecules with chemotherapy drugs, there is need to establish the safety and efficacy of these molecules by performing relevant clinical trials.

The remarkable breakthrough research in molecular biology and advancements in next-generation sequencing (NGS) have significantly enriched our understandings of the epigenetic regulation of gene expression. The advancement in epigenetic research also inspired the scientific interest for investigating the influence of diet on variety of degenerative diseases including cancer. However, the molecular underpinnings underlying these effects are poorly understood. The scientific enquiry as to how dietary ingredients influence epigenetic modifications that eventually regulate health was attributed with catalytic functions of the epigenetic enzymes, which are responsible for “writing” or “erasing” the epigenetic modifications. Voluminous preclinical data suggest that dietary bioactive ingredients modulate the epigenetic landscape by inhibiting/regulating the activity of HDACs, HAT, DNMTs, acetylation/deacetylation, sumyolation, chromatin remodelling, etc. These diet-induced histone modifications regulate the conformational dynamics of chromatin structure, which ultimately leads to changes in DNA accessibility by transcription machinery leading to gene expression. Variety of dietary bioactive molecules found in several foods act as dietary modulators, which alter the epigenetic landscape against the growth and proliferation of cancer. Searching such diet origin anticancer epigenetic modulators and making a consortium of such dietary sources will lead to the formulation of anticancer epigenetic diet.

The serine protease, elastase exists in various forms and plays diverse roles in the human body. Pharmacological inhibition of elastase has been investigated for its therapeutic role in managing conditions such as diabetes, pneumonia and arthritis. Sivelestat, a synthetic molecule, is the only elastase inhibitor to have been approved by any major drug regulatory authority (PMDA, in this case) – but still has failed to attain widespread clinical usage owing to its high price, cumbersome administration and obscure long-term safety profile. In order to find a relatively better-suited alternative, screening was conducted using plant flavonoids, which yielded Baicalein – a molecule that showed robust inhibition against Pancreatic Elastase inhibition (IC50: 3.53 μM). Other than having an IC50 almost 1/5th of that of sivelestat’s, baicalein is also cheaper, safer and easier to administer. While Microscale thermophoresis validated baicalein-elastase interaction, enzyme-kinetic studies, molecular docking and molecular dynamic simulation revealed the mode of inhibition to be non-competitive. Baicalein exhibited binding to a distinct allosteric site on the enzyme. The current study demonstrates the elastase inhibition properties of baicalein in an in-vitro and in-silico environment.

Leishmaniasis is a tropical neglected disease that imposes major health concerns in many endemic countries worldwide and requires urgent attention to the identification of new drug targets as well as drug candidates. In the current study, we propose homoserine kinase (HSK) inhibition as a strategy to induce pathogen mortality via generating threonine deficiency. We introduce a homology-based molecular model of leishmanial HSK that appears to possess all conserved structural as well as functional features in the GHMP kinase family. Furthermore, 200 ns molecular dynamics data of the enzyme in open and closed state attempts to provide the mechanistic details involved in the substrate as well as phosphate binding to this enzyme. We discuss the structural and functional significance of movements involved in various loops (motif 1, 2, 3) and lips (upper and lower) in the transition of leishmanial HSK from closed to open state. Virtual screening data of more than 40,000 compounds from the present investigation tries to identify a few potential HSK inhibitors that possess important features to act as efficient HSK inhibitors. These compounds can be considered an effective starting point for the identification of novel drug-like scaffolds. We hope the structural wealth that is offered in this report will be utilized in designing competent experimental and therapeutic interventions for leishmaniasis management. Graphical abstract.

The health concern of the alcoholic beverages has remained a key issue to be addressed to the consumers. The aim of the present study was to assess the antioxidant activity and cytotoxicity of the selected 22 bottled commercial alcoholic brands widely consumed in the Maharashtra state of India. The result of the present study shows that the brands of wines followed by whiskies and rums were more effective as free radical scavenging agents, containing considerable amount of polyphenols. Overall, the vodaka brands were observed to be more cytotoxic as compared to other brands. With few exceptions, there exists a positive correlation in the amount of polyphenols and free radical scavenging activity, while the former was negatively correlated with cytotoxicity.

Leishmaniasis is one of the most neglected tropical diseases that demand immediate attention to the identification of new drug targets and effective drug candidates. The present study demonstrates the possibility of using threonine synthase (TS) as a putative drug target in leishmaniasis disease management. We report the construction of an effective homology model of the enzyme that appears to be structurally as well as functionally well conserved. The 200 nanosecond molecular dynamics data on TS with and without pyridoxal phosphate (PLP) shed light on mechanistic details of PLP-induced conformational changes. Moreover, we address some important structural and dynamic interactions in the PLP binding region of TS that are in good agreement with previously speculated crystallographic estimations. Additionally, after screening more than 44,000 compounds, we propose 10 putative inhibitor candidates for TS based on virtual screening data and refined Molecular Mechanics Generalized Born Surface Area calculations. We expect that structural and functional dynamics data disclosed in this study will help initiate experimental endeavors toward establishing TS as an effective antileishmanial drug target.

In this study, we report the expeditious synthesis of ten new antifungal and antioxidant agents containing heterocyclic linked 7-arylidene indanone moiety. The solvent-free microwave technique, ample substrate scope, superfast synthesis, and very simple operation are noteworthy features of this protocol. Antifungal activities of the newly synthesized compounds were evaluated against four fungal strains namely Rhizophus oryzae, Mucor mucido, Aspergillus niger, and Candida albicans. Most of the compounds were shown strong inhibition of the investigated fungal agents. In vitro, antioxidant potential against DPPH and OH radicals affirmed that the synthesized compounds are good to excellent radicals scavenging agents. The cytotoxicity data of the synthesized compounds towards HL-60 cells uncovered that the synthesized compounds display very low to negligible cytotoxicity. The structural and quantum chemical parameters of the synthesized compounds were explored by employing density functional theory (DFT) at B3LYP functional using 6-311G(d,p) basis set. The compound 3a is discussed in detail for the theoretical and experimental correlation. Time-dependent density functional theory (TD-DFT) at CAM-B3LYP functional with 6-311G(d,p) basis set was used for the electronic absorption study in the gas phase and indichloromethane and benzene solvents. The UV–Visible absorption peaks and fundamental vibrational wavenumbers were computed and a good agreement between observed and theoretical results has been achieved. From the DFT and antifungal activity correlation, it has been found that the 7-heteroarylidene indanones with more stabilized LUMO energy levels display good antifungal potential.

Diabetes is embracing the human population in logarithmic fashion both in developed as well as developing countries. Aldose reductase is one of the important enzymes of polyol pathway of sugar metabolism in humans. Aldose reductase inhibition has been identified as one of the important target for developing novel antidiabetic agents. In this report, we present an effective synthesis of 7-(substituted phenyl) chromeno-pyrano [2,3-d]pyrimidine-6,8,10-(7H,9H,11H)-trione derivatives and demonstrate their aldose reductase inhibition potential in order to identify novel schemes for finding putative aldose reductase inhibitors. The antioxidant activity of all the synthesized compounds with negligible toxicity demonstrates the biological efficacy of the synthesized compounds. The in silico molecular docking and structural analysis of docked poses conducted in the current investigation sheds light on the structural rationale of the observed aldose reductase inhibition by all the newly synthesized compounds.

There are many online resources that focus on chemical diversity of natural compounds, but only handful of resources exist that focus solely on flavonoid compounds and integrate structural and functional properties; however, extensive collated flavonoid literature is still unavailable to scientific community. Here we present an open access database ‘FlavoDb’ that is focused on providing physicochemical properties as well as topological descriptors that can be effectively implemented in deducing large scale quantitative structure property models of flavonoid compounds. In the current version of database, we present data on 1, 19,400 flavonoid compounds, thereby covering most of the known structural space of flavonoid class of compounds. Moreover, effective structure searching tool presented here is expected to provide an interactive and easy-to-use tool for obtaining flavonoid-based literature and allied information. Data from FlavoDb can be freely accessed via its intuitive graphical user interface made available at following web address: http://bioinfo.net.in/flavodb/home.html.