Modulation of cholesterol metabolism with Phytoremedies in Alzheimer's disease: A comprehensive review.

Alzheimer's disease (AD) is a complex neurological ailment that causes cognitive decline and memory loss. Cholesterol metabolism dysregulation has emerged as a crucial element in AD pathogenesis, contributing to the formation of amyloid-beta (Aß) plaques and tau tangles, the disease's hallmark neuropathological characteristics. Thus, targeting cholesterol metabolism has gained attention as a potential therapeutic method for Alzheimer's disease. Phytoremedies, which are generated from plants and herbs, have shown promise as an attainable therapeutic option for Alzheimer's disease. These remedies contain bioactive compounds like phytochemicals, flavonoids, and polyphenols, which have demonstrated potential in modulating cholesterol metabolism and related pathways. This comprehensive review explores the modulation of cholesterol metabolism by phytoremedies in AD. It delves into the role of cholesterol in brain function, highlighting disruptions observed in AD. Additionally, it examines the underlying molecular mechanisms of cholesterol-related pathology in AD. The review emphasizes the significance of phytoremedies as a potential therapeutic intervention for AD. It discusses the drawbacks of current treatments and the need for alternative strategies addressing cholesterol dysregulation and its consequences. Through an in-depth analysis of specific phytoremedies, the review presents compelling evidence of their potential benefits. Molecular mechanisms underlying phytoremedy effects on cholesterol metabolism are examined, including regulation of cholesterol-related pathways, interactions with Aß pathology, influence on tau pathology, and anti-inflammatory effects. The review also highlights challenges and future perspectives, emphasizing standardization, clinical evidence, and personalized medicine approaches to maximize therapeutic potential in AD treatment. Overall, phytoremedies offer promise as a potential avenue for AD management, but further research and collaboration are necessary to fully explore their efficacy, safety, and mechanisms of action.

Determinants of discomfort from combined exposure to noise and vibration in dumper operators of mining industry in India.

In the mining industry, dumper operators are exposed to combined noise and vibration, leading to discomfort. Dumpers are heavy earth-moving machines that are used for carrying bulky material in mining industries. Dumper operators are exposed to physical hazards such as vibration, noise, heat, and humidity, throughout their lifetime of work. Fifty-four dumper operators working in mines were selected for this study. Noise was measured as per the guidelines of the Directorate General Mining Safety, India, and whole-body vibration was measured as per the guidelines of ISO 2631-1::1997. Noise Pro DLX, Type 2 noise dosimeters were used for the measurement of personal noise exposure while SV-106 six channels vibration meters were used for whole body vibration (WBV) exposure measurement. Discomfort was calculated using the regression equation developed by Huang and Griffin (2014). The total discomfort level of mine operators was about 192. A predictive equation was derived by using a regression model to determine the contribution of individual variables causing discomfort. It was observed that for every unit increase in noise (LAeq), discomfort increased by 10.20 units, a one-unit increase in vibration (A (8)) led to a 51.7-unit increase in discomfort, while an increase of one unit of exposure time increased the discomfort level by 5.24 units.

Agmatine as a novel intervention for Alzheimer's disease: Pathological insights and cognitive benefits.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and a significant societal burden. Despite extensive research and efforts of the multidisciplinary scientific community, to date, there is no cure for this debilitating disease. Moreover, the existing pharmacotherapy for AD only provides symptomatic support and does not modify the course of the illness or halt the disease progression. This is a significant limitation as the underlying pathology of the disease continues to progress leading to the deterioration of cognitive functions over time. In this milieu, there is a growing need for the development of new and more efficacious treatments for AD. Agmatine, a naturally occurring molecule derived from L-arginine, has emerged as a potential therapeutic agent for AD. Besides this, agmatine has been shown to modulate amyloid beta (Aß) production, aggregation, and clearance, key processes implicated in AD pathogenesis. It also exerts neuroprotective effects, modulates neurotransmitter systems, enhances synaptic plasticity, and stimulates neurogenesis. Furthermore, preclinical and clinical studies have provided evidence supporting the cognition-enhancing effects of agmatine in AD. Therefore, this review article explores the promising role of agmatine in AD pathology and cognitive function. However, several limitations and challenges exist, including the need for large-scale clinical trials, optimal dosing, and treatment duration. Future research should focus on mechanistic investigations, biomarker studies, and personalized medicine approaches to fully understand and optimize the therapeutic potential of agmatine. Augmenting the use of agmatine may offer a novel approach to address the unmet medical need in AD and provide cognitive enhancement and disease modification for individuals affected by this disease.

Investigating the Brain Activity Correlates of Humming Bee Sound during Bhramari Pranayama.

Context: Previous research has shown the vast benefits associated with BhP. However, the dynamics of cortical activity in connection with Bhramari sound have not been investigated yet. Aim: To investigate the cortical activity in connection with Bhramari sound. Settings and Design: Humming sound was analyzed with a custom-made nasal device consisting of MAX4466 sensor time synchronized with the EEG setup. We anticipated that the modulation of cortical activity with the humming sound (either of long or short durations) leaves its effects after the Pranayama, which helps to understand the positive impacts of BhP. Methods and Material: 30 participants were instructed to perform the BhP for a period of 90 seconds. We proposed to investigate the cortical correlates before, during, and after the BhP through EEG. A custom-made nasal device consisting of MAX4466 sensor time synchronized with the EEG setup was used for analyzing the humming sound. Statistical Analysis Used: A paired t-test (P < 0.05) with a Bonferroni correction is carried out to explore the statistically significant difference in power spectral density (PSD) values. Results: Results show that the relative spectral power in theta band for short humming durations (less than or equal to 9 seconds) was similar on the frontal cortex during and after the Pranayama practice (P > 0.05) in most of the subjects. Conclusions: In conclusion, for the immediate positive effects of BhP, the humming duration should be kept less than or equal to 9 seconds. A wearable sound recording system can be developed in the future as a feedback system that provides biofeedback to the user so that a constant humming duration can be maintained.

Molecular understanding of ER-MT communication dysfunction during neurodegeneration.

Biological researchers are seeing organelles in a new light. These cellular entities have been believed to be singular and distinctive structures that performed specialized purposes for a very long time. But in recentpast years, scientists have learned that organelles become dynamic and make physical contact. Additionally, Biological processes are regulated by organelles interactions and its alteration play an important role in cell malfunctioning and several pathologies, including neurodegenerative diseases. Mitochondrial-ER contact sites (MERCS) have received considerable attention in the domain of cell homeostasis and dysfunction, specifically in the area of neurodegeneration. This is largely due to the significant role of this subcellular compartment in a diverse array of vital cellular functions, including Ca2+ homeostasis, transport, bioenergetics and turnover, mitochondrial dynamics, apoptotic signaling, ER stress, and inflammation. A significant number of disease-associated proteins were found to physically interact with the ER-Mitochondria (ER-MT) interface, causing structural and/or functional alterations in this compartment. In this review, we summarize current knowledge about the structure and functions of the ER-MT contact sites, as well as the possible repercussions of their alteration in notable neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and fronto-temporal dementia. The constraints and complexities in defining the nature and origin of the highlighted defects in ER-MT communication, as well as their concise contribution to the neurodegenerative process, are illustrated in particular. The possibility of using MERCS as a potential drug target to prevent neuronal damage and ultimately neurodegeneration is the topic of our final discussion.

Mitophagy regulation in aging and neurodegenerative disease.

Mitochondria are the primary cellular energy generators, supplying the majority of adenosine triphosphate through oxidative phosphorylation, which is necessary for neuron function and survival. Mitophagy is the metabolic process of eliminating dysfunctional or redundant mitochondria. It is a type of autophagy and it is crucial for maintaining mitochondrial and neuronal health. Impaired mitophagy leads to an accumulation of damaged mitochondria and proteins leading to the dysregulation of mitochondrial quality control processes. Recent research shows the vital role of mitophagy in neurons and the pathogenesis of major neurodegenerative diseases. Mitophagy also plays a major role in the process of aging. This review describes the alterations that are being caused in the mitophagy process at the molecular level in aging and in neurodegenerative diseases, particularly Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis, also looks at how mitophagy can be exploited as a therapeutic target for these diseases.

Chronic agmatine treatment prevents olanzapine-induced obesity and metabolic dysregulation in female rats.

Antipsychotic-induced obesity affects millions of people and is a serious health condition worldwide. Olanzapine is the most widely prescribed antipsychotic agent with high obesogenic potential. However, the exact mechanism by which it causes its metabolic dysregulation remains poorly understood. In this study, we investigated the effect of agmatine in olanzapine-induced metabolic derangements in Female Sprague-Dawley rats. Repeated olanzapine administration for 28 days increased body weight while treatment with agmatine from days 15 to 28 prevented the body weight gain induced by olanzapine without any alteration in food intake. Repeated agmatine treatment decreased the elevated feeding efficiency and adiposity index, as well as improved dysregulated lipid metabolism induced by olanzapine. Increased activity of fatty acid synthase (FAS) and decreased expression of carnitine palmitoyl transferase-1 (CPT-1) were detected in chronic olanzapine-treated rats. Although agmatine treatment did not alter FAS activity, it increased CPT-1 activity. It is possible that the inhibitory effect of agmatine on weight gain and adiposity might be associated with increased mitochondrial fatty acid oxidation and energy expenditure in olanzapine-treated rats. We suggest that agmatine can be explored for the prevention of obesity complications associated with chronic antipsychotic treatment.

Respirable dust and crystalline silica exposure among different mining sectors in India.

Silicosis is one of the major occupational lung diseases among miners worldwide. The objective of this study was to characterize respirable dust and crystalline silica from limestone, iron, and bauxite mines in India. In total, 86 personal dust samples were collected from limestone (n = 30), iron (n = 30), and bauxite (n = 26) mines using dust sampler. The concentration of crystalline silica was analyzed using FTIR spectroscopy. Geometric mean respirable dust concentrations observed were 0.92, 1.08, and 1.07 mg/m3 for limestone, iron, and bauxite mines respectively, similarly for crystalline silica concentration observations were 0.015, 0.012 and 0.008 mg/m3 respectively. Among the three studied ores, mean crystalline silica concentration was statistically significant (p < 0.05) using an analysis of variance test. Although the detected levels of exposure are within the Indian exposure limits, attention should be paid to lower crystalline silica levels to minimize the risk of silicosis.

Exposure profile of respirable crystalline silica in stone mines in India.

Silicosis is one of the major occupational lung diseases among stone miners; currently, it is a major concern in India given its 12-30% prevalence. The objective of this study was to determine the exposure profile of respirable dust and crystalline silica concentrations from sandstone, masonry stone, and granite stone mines in India. Personal respirable dust samples were collected from each type of mine and analyzed for dust and respirable crystalline silica concentrations. The mean dust concentrations were found to be 0.47 mg/m3, 1.24 mg/m3, and 3.28 mg/m3 for sandstone, masonry stone, and granite stone mines, respectively. The mean respirable crystalline silica concentrations were 0.12 mg/m3 for sandstone mines and 0.17 mg/m3 for masonry stone and granite stone mines. The concentrations in sandstone mines was below the standard stipulated by the Directorate General of Mine Safety in India (0.15 mg/m3), whereas in the granite and masonry mines the concentrations just exceeded the limit. The Indian standard for respirable crystalline silica is three to six times higher than the standard set elsewhere (i.e., by OSHA, ACGIH®, and Egyptian Labor Law standards). Considering the large number of silicosis cases among stone miners in India, the present standard appears inadequate. It is recommended that the standard be lowered to match international standards that minimize the risk of silicosis.

Structural features and oligomeric nature of human podocin domain.

Podocytes are crucial cells of the glomerular filtration unit and plays a vital role at the interface of the blood-urine barrier. Podocyte slit-diaphragm is a modified tight junction that facilitates size and charge-dependent permselectivity. Several proteins including podocin, nephrin, CD2AP, and TRPC6 form a macromolecular assembly and constitute the slit-diaphragm. Podocin is an integral membrane protein attached to the inner membrane of the podocyte via a short transmembrane region (101-125). The cytosolic N- and C-terminus help podocin to attain a hook-like structure. Podocin shares 44% homology with stomatin family proteins and similar to the stomatin proteins, podocin was shown to associate into higher-order oligomers at the site of slit-diaphragm. However, the stoichiometry of the homo-oligomers and how it partakes in the macromolecular assemblies with other slit-diaphragm proteins remains elusive. Here we investigated the oligomeric propensity of a truncated podocin construct (residues:126-350). We show that the podocin domain majorly homo-oligomerizes into a 16-mer. Circular dichroism and fluorescence spectroscopy suggest that the 16-mer oligomer has considerable secondary structure and moderate tertiary packing.

Vaccines for the prevention of recurrent urinary tract infections: a systematic review.

OBJECTIVES: To systematically review the evidence regarding the efficacy of vaccines or immunostimulants in reducing the recurrence rate of urinary tract infections (UTIs). MATERIALS AND METHODS: The Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), PubMed, Cochrane Library, World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal, and conference abstracts were searched up to January 2018 for English-titled citations. Randomised placebo-controlled trials evaluating UTI recurrence rates in adult patients with recurrent UTIs treated with a vaccine were selected by two independent reviewers according to the Population, Interventions, Comparators, and Outcomes (PICO) criteria. Differences in recurrence rates in study populations for individual trials were calculated and pooled, and risk ratios (RRs) using random effects models were calculated. Risk of bias was assessed using the Cochrane Collaboration's tool and heterogeneity was assessed using chi-squared and I2 testing. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of evidence (QOE) and summarise findings. RESULTS: In all, 599 records were identified, of which 10 studies were included. A total of 1537 patients were recruited and analysed, on whom data were presented. Three candidate vaccines were studied: Uro-Vaxom® (OM Pharma, Myerlin, Switzerland), Urovac® (Solco Basel Ltd, Basel, Switzerland), and ExPEC4V (GlycoVaxyn AG, Schlieren, Switzerland). At trial endpoint, the use of vaccines appeared to reduce UTI recurrence compared to placebo (RR 0.74, 95% confidence interval [CI] 0.67-0.81; low QOE). Uro-Vaxom showed the greatest reduction in UTI recurrence rate; the maximal effect was seen at 3 months compared with 6 months after initial treatment (RR 0.67, 95% CI 0.57-0.78; and RR 0.78, 95% CI 0.69-0.88, respectively; low QOE). Urovac may also reduce risk of UTI recurrence (RR 0.75, 95% CI 0.63-0.89; low QOE). ExPEC4V does not appear to reduce UTI recurrence compared to placebo at study endpoint (RR 0.82, 95% CI 0.62-1.10; low QOE). Substantial heterogeneity was observed across the included studies (chi-squared = 54.58; P < 0.001, I2  = 84%). CONCLUSIONS: While there is evidence for the efficacy of vaccines in patients with recurrent UTIs, significant heterogeneity amongst these studies renders interpretation and recommendation for routine clinical use difficult at present. Further randomised trials using consistent definitions and endpoints are needed to study the long-term efficacy and safety of vaccines for infection prevention in patients with recurrent UTIs.

Antioxidant, anti-inflammatory, and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives.

The synthesized flavonoid derivatives were examined for their antioxidant, anti-inflammatory, xanthine oxidase (XO), urease inhibitory activity, and cytotoxicity. Except few, all the flavonoids under this study showed significant antioxidant activity (45.6%-85.5%, 32.6%-70.6%, and 24.9%-65.5% inhibition by DPPH, ferric reducing/antioxidant power, and oxygen radical absorption capacity assays) with promising TNF-α inhibitory activity (42%-73% at 10 µM) and IL-6 inhibitory activity (54%-81% at 10 µM) compared with that of control dexamethasone. The flavonoids luteolin, apigenin, diosmetin, chrysin, O3Ꞌ , O7 -dihexyl diosmetin, O4Ꞌ , O7 -dihexyl apigenin, and O7 -hexyl chrysin, showed an inhibition with IC50 values (4.5-8.1 µg/mL), more than allopurinol (8.5 µg/mL) at 5 µM against XO and showing more than 50% inhibition at a final concentration (5 mM) with an IC50 value of ranging from 4.8 to 7.2 (µg/mL) in comparison with the positive control thiourea (5.8 µg/mL) for urease inhibition. Thus, the flavonoid derivatives may be considered as potential antioxidant and antigout agents.

Epidemiological and survival analysis of triple-negative breast cancer cases in a retrospective multicenter study.

INTRODUCTION: This is a retrospective study with data collected from breast cancer cases from five major Apollo Hospitals across India, as part of a biobanking process. One aspect of our study focused specifically on data from triple-negative breast cancer (TNBC) cases. The aim of this study was to analyze epidemiology, treatment options, and survival of the patients with TNBC. Our goal was to draw conclusions on the preponderance of the disease and also to understand the outcomes using the existing therapy options. MATERIALS AND METHODS: Data were collected after due ethical clearances and were coded with regard to patient identifiers to protect patient privacy. Data were not only from the various departments of the respective hospitals and the treating physicians but also from the follow-up made by hospital staff and social workers. RESULTS: About 20% of all cases of breast cancer comprised TNBC. Although the disease is generally thought to be an early onset disease, there was no major difference in the median age of diagnosis of TNBC compared to other breast cancer cases. More than 85% of the TNBC cases were of early stage disease with <4% of the cases of metastatic cancer. Data on follow-up were somewhat sporadic as a good number of cases were lost to follow-up, but from the available data, recurrence rate was about 11%. Death, when it occurred, was mostly in the early periods of treatment with 35% of the events occurring before 3 years. The overall survival rates beyond 3 years were more than 86%. CONCLUSIONS: Data and sample collection are an ongoing process, so we expect this data set to be enriched with more cases and longer duration of follow-up in a year. Preliminary analysis sheds light on the potential of such a collection both for understanding the epidemiology of the disease and also for conducting future studies with an eye toward improving treatment outcomes.

Serratiopeptidase Niosomal Gel with Potential in Topical Delivery.

The objective of present study was to develop nonionic surfactant vesicles of proteolytic enzyme serratiopeptidase (SRP) by adapting reverse phase evaporation (REV) technique and to evaluate the viability of SRP niosomal gel in treating the topical inflammation. The feasibility of SRP niosomes by REV method using Span 40 and cholesterol has been successfully demonstrated in this investigation. The entrapment efficiency was found to be influenced by the molar ratio of Span 40 : cholesterol and concentration of SRP in noisome. The developed niosomes were characterized for morphology, particle size, and in vitro release. Niosomal gel was prepared by dispersing xanthan gum into optimized batch of SRP niosomes. Ex vivo permeation and in vivo anti-inflammatory efficacy of gel formulation were evaluated topically. SRP niosomes obtained were round in nanosize range. At Span 40 : cholesterol molar ratio 1 : 1 entrapment efficiency was maximum, that is, 54.82% ± 2.08, and showed consistent release pattern. Furthermore ex vivo skin permeation revealed that there was fourfold increase in a steady state flux when SRP was formulated in niosomes and a significant increase in the permeation of SRP, from SRP niosomal gel containing permeation enhancer. In vivo efficacy studies indicated that SRP niosomal gel had a comparable topical anti-inflammatory activity to that of dicolfenac gel.

Synthesis and biological evaluation of asymmetric indole curcumin analogs as potential anti-inflammatory and antioxidant agents.

Abstract A series of asymmetric indole curcumin analogs were synthesized and evaluated as possible inhibiters of pro-inflammatory enzymes such as COX-2, pro-inflammatory cytokines as TNF-α and IL-6, trypsin and ß-glucuronidase. They were also tested for antioxidant activities. The results showed that compounds 5e and 5h were found to be the most potent inhibitors of COX-2 (83.33%, 82.50%) and ß-glucuronidase (67.80%, 64.12%). All the synthesized compounds exhibited promising activity against IL-6 in a range of 71-100% at 10 µM concentration. Compounds 5f, 5h, 5e, 5c and 5d showed significant inhibition against TNF-α (28-51%) and IL-6 (87-98%) with low toxicity (45-51%) against CCK-8 cells. With few exceptions, all other compounds were found to be good to excellent inhibitors of IL-6 and moderate inhibitors of TNF-α; however, the toxicity profiles of these compounds need to be ameliorated in further optimization studies. Amongst the tested compounds, 5c, 5b, 5j and 5g were found to possess excellent reducing activity and 5b, 5c and 5h were moderate DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavengers.

Synthesis of novel carbazole chalcones as radical scavenger, antimicrobial and cancer chemopreventive agents.

A series of novel carbazole chalcones has been synthesised and evaluated for radical scavenging activity, cytotoxicity and antimicrobial activities. Compounds 12m, 12o and 12c exhibited good 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, compounds 12e, 12m and 12d were excellent hydroxyl radical scavengers and compounds 12a, 12e, 12g, 12n and 12m have shown inhibition of oxidative DNA damage induced by 2,2'-azobis (2-amidinopropane hydrochloride). Compounds 12j, 12i, 12n, 12c, 12m and 12e were most active against the selected cancer cell lines. Compounds 12a, 12e and 12m showed good antibacterial activity and compounds 12h and 12m have shown good antifungal activity. All the compounds were subjected for absorption, distribution, metabolism and excretion (ADME) predictions by computational method and found that these molecules could be considered as potential candidates for oral drug development.

Synthesis and biological evaluation of novel series of aminopyrimidine derivatives as urease inhibitors and antimicrobial agents.

A novel series of carbazole substituted aminopyrimidines (5a-p) were synthesized and screened for their in vitro urease inhibition and antimicrobial activity. Among the compounds, 4-(2,4-dichlorophenyl)-6-(9-methyl-9H-carbazol-3-yl)-pyrimidin-2-amine (5i) was found to be the most potent showing urease inhibitory activity with an IC50 value 19.4 ± 0.43 µM. Compounds 5c, 5g, 5j and 5o showed good activity against all selected bacterial strains and compounds 5b, 5c, 5m and 5o showed good activity against selected fungal strains. All the compounds were subjected for ADME predictions by computational method.

Synthesis, biological evaluation, and docking studies of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines as potent anti-inflammatory and antioxidant agents.

A novel series of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines (5a-o) has been synthesized and the structures of newly synthesized compounds were characterized by IR, (1)H NMR and mass spectral analysis. All the synthesized compounds were evaluated for their in vitro and in vivo anti-inflammatory activity, and also for their antioxidant activity. Compounds 5b, 5c, 5d and 5n were found to be selective COX-2 inhibitors. Compound 5c was found to potent inhibitor of the carrageenin induced paw edema in rats. Most of the compounds exhibited good DPPH and superoxide radical scavenging activity, while compounds 5c, 5d, 5i and 5k exhibited good hydroxyl radical scavenging activity. Molecular docking result, along with the biological assay data, suggested that compound 5c was a potential anti-inflammatory agent.

Synthesis, biological evaluation, and molecular docking of N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives as xanthine oxidase and tyrosinase inhibitors.

Claisen-Schmidt condensation of 3-formyl-9-methylcarbazole with various amides of 3-aminoacetophenone afforded N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives. All compounds were investigated for their in vitro xanthine oxidase (XO), tyrosinase and melanin production inhibitory activity. Most of the target compounds had more potent XO inhibitory activity than the standard drug (IC(50) = 4.3-5.6 µM). Interestingly, compound 7q bearing cyclopropyl ring was found to be the most potent inhibitor of XO (IC(50) = 4.3 µM). Molecular modelling study gave an insight into its binding modes with XO. Compounds 7a, 7d, 7e, 7g, and 7k were found to be potent inhibitors of tyrosinase (IC(50) = 14.01-17.52 µM). These results suggest the possible use of these compounds for the design and development of novel XO and tyrosinase inhibitors.

Synthesis and antioxidant, cytotoxicity and antimicrobial activities of novel curcumin mimics.

Claisen-Schmidt condensation of 3-(1,2,3,6-tetrahydro-1-methylpyridin-4-yl)-2,4,5- trimethoxybenzaldehyde 3 and various aromatic, heterocyclic and alicyclic amides of 3- aminoacetophenone 6(a-s) afforded novel curcumin mimics. All the synthesized compounds were characterized by IR, (1)H NMR, Mass spectroscopy and evaluated for antioxidant, cytotoxicity and antimicrobial activity. Out of the 20 compounds screened, compounds 7i, 7l, 7q, and 7n have shown excellent radical scavenging activity, compounds 7o, 7t, 7f, and 7r have shown significant xanthine oxidase inhibition, and compounds 7a, 7k and 7l were found to be potent inhibitors of selected cancer cell lines. Compounds 7h, 7t, 7l, 7i, and 7e have shown good antibacterial activity, whereas compounds 7j, 7f, 7o, 7h, and 7t exhibited significant antifungal activity.