Marine Based Natural Products: Exploring the Recent Developments in the Identification of Antimicrobial Agents.

The marine ecosystem is the less explored, biologically diverse, and vastest resource to discover novel antimicrobial agents. In recent decades' antimicrobial drugs are losing their effectiveness due to the growing resistance among pathogens, which causes diseases to have considerable death rates across the globe. Therefore, there is a need for the discovery of new antibacterials that can reach the market. There is a gradual growth of compounds from marine sources which are entering the clinical trials. Thus, the prominence of marine natural products in the field of drug design and discovery across the academia and pharmaceutical industry is gaining attention. Herein, the present review covers nearly 200 marine based antimicrobial agents of 11 structural classes discovered from the year 2010 to 2022. All the discussed compounds have exhibited medium to high antimicrobial activity in inhibiting various microorganisms.

Comprehensive Analysis of Secondary Metabolites in Usnea longissima (Lichenized Ascomycetes, Parmeliaceae) Using UPLC-ESI-QTOF-MS/MS and Pro-Apoptotic Activity of Barbatic Acid.

Considering the importance of ultra-performance liquid chromatography-electrospray ionization-quadrupole time of flight-tandem mass spectrometry (UPLC-ESI-QTOF-MS/MS) hyphenated techniques for analysis of secondary metabolites from crude extracts, the present study was aimed at identification of secondary metabolites in acetone extract of the lichen Usnea longissima. From our study, 19 compounds were tentatively identified through comparison of exact molecular masses from their MS/MS spectra, mass fragmentation studies and comparison with literature data. In addition, potent cytotoxic activity of U. longissima extract prompted us to isolate four compounds, 18R-hydroxy-dihydroalloprotolichesterinic acid (19), neuropogolic acid (20), barbatic acid (21), and usnic acid (22) from this extract which were adequately identified through mass spectrometry and NMR spectroscopy. All four compounds displayed cytotoxic activity. Barbatic acid (21) manifested doxorubicin equivalent activity against A549 lung cancer cell line with IC50 of 1.78 µM and strong G0/G1 accumulation of cells. Poly ADP-ribose polymerase (PARP) cleavage confirmed that it induced cytotoxic activity via apoptosis. Finally, our work has discerned the depside, barbatic acid (21) from crude extract as a candidate anti-cancer molecule, which induces cell death by stepping up apoptosis.

Minor Pyranonaphthoquinones from the Apothecia of the Lichen Ophioparma ventosa.

Four new quinonoid naphthopyranones, ophioparmin (1), 4-methoxyhaemoventosins (2a and 2b), and 4-hydroxyhaemoventosin (3), together with anhydrofusarubin lactone (4) and haemoventosin (5) were isolated from the fruiting bodies of Ophioparma ventosa, a crustose lichen. Their structures were determined by spectroscopic analyses, and the absolute configurations of 1 and 2 were elucidated through experimental and calculated electronic circular dichroism analyses. Compounds 1, 2, and 5 exhibited moderate to strong antioxidant activities. The main pigment haemoventosin exhibited significant cytotoxicity toward a panel of nine cell lines.

Inhaled corticosteroids in chronic obstructive pulmonary disease: a pro-con perspective.

Current guidelines limit regular use of inhaled corticosteroids (ICS) to a specific subgroup of patients with chronic obstructive pulmonary disease (COPD) in whom the forced expiratory volume in 1 s is <60% of predicted and who have frequent exacerbations. In these patients, there is evidence that ICS reduce the frequency of exacerbations and improve lung function and quality of life. However, a review of the literature suggests that the evidence available may be interpreted to favour or contradict these observations. It becomes apparent that COPD is a heterogeneous condition. Clinicians therefore need to be aware of the heterogeneity as well as having an understanding of how ICS may be used in the context of the specific subgroups of patients with COPD. This review argues for and against the use of ICS in COPD by providing an in-depth analysis of the currently available evidence.

Limonoids from the leaves of Soymida febrifuga and their insect antifeedant activities.

Three new phragmalin-type limonoids (1-3) were isolated from the leaves of Soymida febrifuga together with thirteen known limonoids. The structures of these compounds were established on the basis of spectroscopic data. All these isolates were evaluated for their anti-feedant activities in tobacco caterpillar (Spodoptera litura) and castor semilooper (Achaea janata) using a no-choice laboratory bioassay. Among the tested, compounds 9 and 15 demonstrated the potent anti-feedant index (76.46 µg/cm(2), 66.61 µg/cm(2) against A. janata, and 61.69 µg/cm(2), 51.93 µg/cm(2)against S. litura).

Bioactive constituents from Tinospora cordifolia (willd.): Isolation, synthesis and their immunomodulatory activity.

Traditional medicinal plants have been used for centuries for their immunomodulatory properties and therapeutic potentials. The present study aims to investigate the immunomodulatory constituents from traditional medicinal plant, Tinospora cordifolia (willd.). Our study resulted in the isolation of new compound, 27-hydroxy octacosyl ferulate (1) along with eleven known compounds (2-12). The structures of the isolated compounds were characterized by combination of NMR (1D and 2D) and Mass spectroscopic methods. The hemisynthesis of compound 12 (ferulic acid) yielded (12a-12d and 12e-12 m) derivatives. Further, the isolated compounds and synthesized derivatives were assessed for their immunomodulatory potentials by evaluating their cytotoxicity and pro-inflammatory effects against macrophage cells (IL-6) and DC activation markers (CD 11c and 86). The biological results indicated that crude extract displayed potent immunomodulatory activity while isolated compounds and synthetic analogues showed moderate activity. Among the tested compounds, new compound (1), quercetin (10) and derivatives 12b, 12c found to be non-cytotoxic and displayed immunomodulatory potentials. Therefore, these compounds can be studied for autoimmunity and other immune suppressing conditions.

Synthesis, anticancer, and antibacterial activities of piplartine derivatives on cell cycle regulation and growth inhibition.

A series of piplartine derivatives were synthesized via Baylis-Hillman reaction and evaluated for anticancer and antibacterial activities. The cytotoxicity of these compounds was examined in two different human tumor cell lines, IMR-32 and HeLa. The antibacterial activity was examined in Staphylococcus aureus and Pseudomonas aeruginosa. The results showed that compounds 2b, 2e, and 2j were found to be the most active compounds, which displayed line no cytotoxicity, but G2-M cell cycle arrest in tumor cells, and showed cytostatic effects in bacteria.

Nanotechnological synergy of mangiferin and curcumin in modulating PI3K/Akt/mTOR pathway: a novel front in ovarian cancer precision therapeutics.

Background: Ovarian cancer, colloquially termed the "silent killer" among gynecological malignancies, remains elusive due to its often-asymptomatic progression and diagnostic challenges. Central to its pathogenesis is the overactive PI3K/Akt/mTOR signaling pathway, responsible for various cellular functions, from proliferation to survival. Within this context, the phytochemical compounds mangiferin (derived from Mangifera indica) and curcumin (from Curcuma longa) stand out for their potential modulatory effects. However, their inherent bioavailability challenges necessitate innovative delivery systems to maximize therapeutic benefits. Objective: This study seeks to synergize the merits of nanotechnology with the therapeutic properties of mangiferin and curcumin, aiming to bolster their efficacy against ovarian cancer. Methods: Employing specific nanotechnological principles, we engineered exosomal and liposomal nano-carriers for mangiferin and curcumin, targeting the PI3K/Akt/mTOR pathway. Molecular docking techniques mapped the interactions of these phytochemicals with key proteins in the pathway, analyzing their binding efficiencies. Furthermore, molecular dynamics simulations, spanning 100 nanoseconds, verified these interactions, with additional computational methodologies further validating our findings. The rationale for the 100 nanoseconds time span lies in its sufficiency to observe meaningful protein-ligand interactions and conformational changes. Notably, liposomal technology provided an enhancement in drug delivery by protecting these compounds from degradation, allowing controlled release, and improving cellular uptake. Results: Our computational investigations demonstrated notable binding affinities of mangiferin and curcumin: PI3K at -11.20 kcal/mol, Akt at -15.16 kcal/mol, and mTOR at -10.24 kcal/mol. The adoption of exosome/liposome-mediated delivery significantly amplified the bioavailability and cellular uptake of these nano-formulated compounds, positioning them as potential stalwarts in ovarian cancer intervention. A brief explanation of exosome/liposome-mediated delivery involves the use of these vesicles to encapsulate and transport therapeutic agents directly to the target cells, enhancing drug delivery efficiency and minimizing side effects. Conclusion: Addressing ovarian cancer's intricacies, dominated by the erratic PI3K/Akt/mTOR signaling, mandates innovative therapeutic strategies. Our pioneering approach converges nanotechnological liposomal delivery with mangiferin and curcumin's natural efficacies. This confluence, validated by computational insights, heralds a paradigm shift in ovarian cancer treatment. As our findings underscore the collaborative potential of these phytochemicals, it beckons further exploration in translational studies and clinical applications, ensuring the best intersection of nature and technology for therapeutic advantage.

Synthesis and biological evaluation of 1,2,3-triazole hybrids of 4-methoxy ethyl cinnamate isolated from Hedychium spicatum (Sm) rhizomes: identification of antiproliferative lead actives against prostate cancer.

A series of 1, 2, 3- triazole hybrids (9a-9n) were synthesised from major phenolic constituent, 4-methoxy ethyl cinnamate (5) isolated from rhizomes of Hedychium spicatum (Sm), a traditional medicinal plant used in variety of disease conditions. All the synthesised analogues were tested for their in vitro antiproliferative potential against HCT 116 (colon cancer), A549 (lung cancer), DU-145 (prostate cancer), Hep G2 (hepatoma) and HEK-293 (normal) cell lines. Among the compounds tested, compounds 9i and 9k potently arrested proliferation of DU-145 (prostate cancer) cell line. Compound 9i displayed 20 times better antiproliferative potential than parent compound and almost identical inhibitory activity to that of the standard drug, doxorubicin. The flow cytometric analysis revealed that 9i arrested cells in G2/M phase of cell cycle and induced apoptosis. Overall, the hybrid derivative 9i was found to be a potential antiproliferative lead against prostate cancer.

Synthesis of novel thiazoles bearing lupeol derivatives as potent anticancer and anti-inflammatory agents.

Lupeol is one of the most important metabolite in the class of terpenoids and possess excellent anticancer, anti-inflammatory, anti-diabetic activities etc. In the present study, the different thiazoles and oxazoles bearing lupeol derivatives were prepared to enhance their biological activity. Initially, the in vitro cytotoxic activity results showed that the synthesized lupeol derivatives (9a-9j and 10a-10e) showed significant activity against various cancer cells and the compounds 9h and 10b exhibited excellent activity against CAL27 cells. Further, these compounds 9h and 10b arrest the cell cycle at S phase and induce the late apoptosis in CAL27 cells by downregulating the BcL2 and vimentin expression and upregulating the Bax gene expression. Moreover, the lupeol derivatives showed dose-dependent anti-inflammatory activity by inhibiting the secretion of IL-6 cytokines in LPS-induced Raw 264.7 cells. Together, these results clearly indicated that the thiazoles and oxazoles bearing lupeol derivatives can used as chemotherapeutic drugs against cancer and inflammatory diseases.

Synthesis and antiproliferative activities of novel piscidinol a derivatives as potential anticancer agents.

Piscidinol A (1), a major compound isolated from Aphanamixis polystachya, showed modest anticancer activity against cancer cell lines. Subsequently, a series of analogues were synthesised by modification of the key structural functionalities of this high yield natural product and assessed for their anticancer potential against various cancer cell lines. Among the tested derivatives, the compounds 6e and 6i are significantly reduced the cell viability at 5.38 and 5.02 µM against DU145 prostate cancer cells, respectively. Additionally, both the compounds arrested the cell cycle at S phase and induced the late apoptosis in DU145 cells. Together, the results demonstrated that the compounds 6e and 6i could be a promising lead for the development of anticancer agents against DU145 and well worth further investigation aiming to generate potential anticancer agents.

Unveiling a novel terpolymer-metal complex: A detailed exploration of synthesis, characterization, and its potential as an antimicrobial and antioxidant agent.

In an innovative approach to push the boundaries of antimicrobial and antioxidant strategies, we present the synthesis and characterization of a novel terpolymer derived from N-Phenyl-p-phenylenediamine and 2-aminopyrimidine with formaldehyde in the presence of dimethylformamide as a reaction medium through polycondensation technique. Leveraging this terpolymer as a ligand, we introduce an intriguing terpolymer-metal complex, created with Ni (II) metal ion. In our pursuit to validate the structure and properties of these substances, we performed meticulous characterizations using important spectral studies such as FTIR, electronic, and 1H NMR spectroscopy. This provided us with a unique fingerprint for the (N-Phenyl-p-phenylenediamine-2-aminopyrimidine-formaldehyde) terpolymeric ligand (PAF) and its metal complex. In addition, the molecular weights of PAF terpolymer were established using gel permeation chromatography. Upon investigation, PAF terpolymer and PAF-Ni complex exhibited impressive antimicrobial activity, tested by the disc-diffusion technique. Both demonstrated potency against a range of harmful bacterial and fungal strains, including Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger. In an extension to their biological applications, we evaluated the free radical scavenging activity of PAF terpolymer and PAF-Ni complex using the DPPH assay. The complex PAF-Ni showcased an enhanced scavenging activity 73.94% (IC50 = 17.58) compared to the ligand PAF 63.06% (IC50 = 27.61) at 100 µg/ml indicating its potential role in oxidative stress management.

Plant HDAC inhibitor chrysin arrest cell growth and induce p21WAF1 by altering chromatin of STAT response element in A375 cells.

BACKGROUND: Chrysin and its analogues, belongs to flavonoid family and possess potential anti-tumour activity. The aim of this study is to determine the molecular mechanism by which chrysin controls cell growth and induce apoptosis in A375 cells. METHODS: Effect of chrysin and its analogues on cell viability and cell cycle analysis was determined by MTT assay and flowcytometry. A series of Western blots was performed to determine the effect of chrysin on important cell cycle regulatory proteins (Cdk2, cyclin D1, p53, p21, p27). The fluorimetry and calorimetry based assays was conducted for characterization of chrysin as HDAC inhibitor. The changes in histone tail modification such as acetylation and methylation was studied after chrysin treatment was estimated by immuno-fluorescence and western blot analysis. The expression of Bcl-xL, survivin and caspase-3 was estimated in chrysin treated cells. The effect of chrysin on p21 promoter activity was studied by luciferase and ChIP assays. RESULTS: Chrysin cause G1 cell cycle arrest and found to inhibit HDAC-2 and HDAC-8. Chrysin treated cells have shown increase in the levels of H3acK14, H4acK12, H4acK16 and decrease in H3me2K9 methylation. The p21 induction by chrysin treatment was found to be independent of p53 status. The chromatin remodelling at p21WAF1 promoter induces p21 activity, increased STAT-1 expression and epigenetic modifications that are responsible for ultimate cell cycle arrest and apoptosis. CONCLUSION: Chrysin shows in vitro anti-cancer activity that is correlated with induction of histone hyperacetylation and possible recruitment of STAT-1, 3, 5 proteins at STAT (-692 to -684) region of p21 promoter. Our results also support an unexpected action of chrysin on the chromatin organization of p21WAF1 promoter through histone methylation and hyper-acetylation. It proposes previously unknown sequence specific chromatin modulations in the STAT responsive elements for regulating cell cycle progression negatively via the induction of the CDK inhibitor p21WAF1.

Light Weighted Healthcare CNN Model to Detect Prostate Cancer on Multiparametric MRI.

The SEMRCNN model is proposed for autonomously extracting prostate cancer locations from regions of multiparametric magnetic resonance imaging (MP-MRI). Feature maps are explored in order to provide fine segmentation based on the candidate regions. Two parallel convolutional networks retrieve these maps of apparent diffusion coefficient (ADC) and T2W images, which are then integrated to use the complimentary information in MP-MRI. By utilizing extrusion and excitation blocks, it is feasible to automatically increase the number of relevant features in the fusion feature map. The aim of this study is to study the current scenario of the SE Mask-RCNN and deep convolutional network segmentation model that can automatically identify prostate cancer in the MP-MRI prostatic region. Experiments are conducted using 140 instances. SEMRCNN segmentation of prostate cancer lesions has a Dice coefficient of 0.654, a sensitivity of 0.695, a specificity of 0.970, and a positive predictive value of 0.685. SEMRCNN outperforms other models like as V net, Resnet50-U-net, Mask-RCNN, and U network model for prostate cancer MP-MRI segmentation. This approach accomplishes fine segmentation of lesions by recognizing and finding potential locations of prostate cancer lesions, eliminating interference from surrounding areas, and improving the learning of the lesions' features.

Supervised Computer-Aided Diagnosis (CAD) Methods for Classifying Alzheimer's Disease-Based Neurodegenerative Disorders.

Alzheimer's disease is incurable at the moment. If it can be appropriately diagnosed, the correct treatment can postpone the patient's illness. To aid in the diagnosis of Alzheimer's disease and to minimize the time and expense associated with manual diagnosis, a machine learning technique is employed, and a transfer learning method based on 3D MRI data is proposed. Machine learning algorithms can dramatically reduce the time and effort required for human treatment of Alzheimer's disease. This approach extracts bottleneck features from the M-Net migration network and then adds a top layer to supervised training to further decrease the dimensionality and delete portions. As a consequence, the transfer network presented in this study has several advantages in terms of computational efficiency and training time savings when used as a machine learning approach for AD-assisted diagnosis. Finally, the properties of all subject slices are combined and trained in the classification layer, completing the categorization of Alzheimer's disease symptoms and standard control. The results show that this strategy has a 1.5 percentage point better classification accuracy than the one that relies exclusively on VGG16 to extract bottleneck features. This strategy could cut the time it takes for the network to learn and improve its ability to classify things. The experiment shows that the method works by using data from OASIS. A typical transfer learning network's classification accuracy is about 8% better with this method than with a typical network, and it takes about 1/60 of the time with this method.

Improved Capsule Network Optimization Hierarchical Convolution Algorithm for Mental Health Recognition.

To address the shortcomings of standard convolutional neural networks (CNNs), the model structure is complex, the training period is lengthy, and the data processing technique is single. A modified capsule network is presented to optimize hierarchical convolution-the algorithm for identifying mental health conditions. To begin, two types of data processing are performed on the original vibration data: wavelet noise reduction and wavelet packet noise reduction; this retains more valuable information for mental health identification in the original signal; secondly, the CNN employs the concept of hierarchical convolution, and three distinct scaled convolution kernels are utilized to extract features from numerous angles; ultimately, the convolution kernel's extracted features are fed into the pruning strategy's capsule network for mental health diagnosis. The enhanced capsule network has the potential to significantly speed up mental health identification while maintaining accuracy. It is time to address the issue of the CNN structure being too complex and the recognition impact being inadequate. The experimental findings indicate that the suggested algorithm achieves a high level of recognition accuracy while consuming a small amount of time.

Convolutional neural network based CT scan classification method for COVID-19 test validation.

Given the novel corona virus discovered in Wuhan, China, in December 2019, due to the high false-negative rate of RT-PCR and the time-consuming to obtain the results, research has proved that computed tomography (CT) has become an auxiliary One of the essential means of diagnosis and treatment of new corona virus pneumonia. Since few COVID-19 CT datasets are currently available, it is proposed to use conditional generative adversarial networks to enhance data to obtain CT datasets with more samples to reduce the risk of over fitting. In addition, a BIN residual block-based method is proposed. The improved U-Net network is used for image segmentation and then combined with multi-layer perception for classification prediction. By comparing with network models such as AlexNet and GoogleNet, it is concluded that the proposed BUF-Net network model has the best performance, reaching an accuracy rate of 93%. Using Grad-CAM technology to visualize the system's output can more intuitively illustrate the critical role of CT images in diagnosing COVID-19. Applying deep learning using the proposed techniques suggested by the above study in medical imaging can help radiologists achieve more effective diagnoses that is the main objective of the research. On the basis of the foregoing, this study proposes to employ CGAN technology to augment the restricted data set, integrate the residual block into the U-Net network, and combine multi-layer perception in order to construct new network architecture for COVID-19 detection using CT images. -19. Given the scarcity of COVID-19 CT datasets, it is proposed that conditional generative adversarial networks be used to augment data in order to obtain CT datasets with more samples and therefore lower the danger of overfitting.

Practical and efficient approach to the synthesis of guineensine.

A total synthesis of guineensine, a secondary metabolite of the Piperaceae family, has been executed in 12 steps with an overall yield of 27%. Key steps in the synthesis featured novel application of a Julia-Kocienski olefination reaction which effectively constructed alkenamide skeleton. This contributes a unique approach to the synthesis of the piperamide alkaloids.

Two new cytotoxic labdane diterpenes from the rhizomes of Hedychium coronarium.

The phytochemical investigation of the hexane extract of the Hedychium coronarium led to the isolation and identification of two new labdane diterpenes (1 and 2) along with 10 known metabolites (3-12). The structures of the new compounds were established on the basis of spectroscopic data analysis (1D and 2D NMR and MS). Cytotoxic activities of the isolates were studied against the A-549 (lung cancer), SK-N-SH (human neuroblastoma), MCF-7 (breast cancer) and HeLa (cervical cancer) cell lines.