Skin emitted volatiles analysis for noninvasive diagnosis: the current advances in sample preparation techniques for biomedical application.

Human skin emits a series of volatile compounds from the skin due to various metabolic processes, microbial activity, and several external factors. Changes in the concentration of skin volatile metabolites indicate many diseases, including diabetes, cancer, and infectious diseases. Researchers focused on skin-emitted compounds to gain insight into the pathophysiology of various diseases. In the case of skin volatolomics research, it is noteworthy that sample preparation, sampling protocol, analytical techniques, and comprehensive validation are important for the successful integration of skin metabolic profiles into regular clinical settings. Solid-phase microextraction techniques and polymer-based active sorbent traps were developed to capture the skin-emitted volatile compounds. The primary advantage of these sample preparation techniques is the ability to efficiently and targetedly capture skin metabolites, thus improving the detection of the biomarkers associated with various diseases. In further research, polydimethyl-based patches were utilized for skin research due to their biocompatibility and thermal stability properties. The microextraction sampling tools coupled with high sensitive Gas Chromatography-Mass Spectrometer provided a potential platform for skin volatolomes, thus emerging as a state-of-the-art analytical technique. Later, technological advancements, including the design of wearable sensors, have enriched skin-based research as it can integrate the information from skin-emitted volatile profiles into a portable platform. However, individual-specific hydration, temperature, and skin conditions can influence variations in skin volatile concentration. Considering the subject-specific skin depth, sampling time standardization, and suitable techniques may improve the skin sampling techniques for the potential discovery of various skin-based marker compounds associated with diseases. Here, we have summarised the current research progress, limitations, and technological advances in skin-based sample preparation techniques for disease diagnosis, monitoring, and personalized healthcare applications.

Natural product-inspired synthesis of coumarin-chalcone hybrids as potential anti-breast cancer agents.

Twelve novel neo-tanshinlactone-chalcone hybrid molecules were constructed through a versatile methodology involving the Horner-Wadsworth-Emmons (HWE) olefination of 4-formyl-2H-benzo [h]chromen-2-ones and phosphonic acid diethyl esters, as the key step, and evaluated for anticancer activity against a series of four breast cancers and their related cell lines, viz. MCF-7 (ER + ve), MDA-MB-231 (ER-ve), HeLa (cervical cancer), and Ishikawa (endometrial cancer). The title compounds showed excellent to moderate in vitro anti-cancer activity in a range of 6.8-19.2 µM (IC50). Compounds 30 (IC50 = 6.8 µM and MCF-7; IC50 = 8.5 µM and MDA-MB-231) and 31 (IC50 = 14.4 µM and MCF-7; IC50 = 15.7 µM and MDA-MB-231) exhibited the best activity with compound 30 showing more potent activity than the standard drug tamoxifen. Compound 30 demonstrated a strong binding affinity with tumor necrosis factor α (TNF-α) in molecular docking studies. This is significant because TNFα is linked to MCF-7 cancer cell lines, and it enhances luminal breast cancer cell proliferation by upregulating aromatase. Additionally, virtual ADMET studies confirmed that hybrid compounds 30 and 31 met Lipinski's rule; displayed high bioavailability, excellent oral absorption, favorable albumin interactions, and strong penetration capabilities; and improved blood-brain barrier crossing. Based on the aforementioned results, compound 30 has been identified as a potential anti-breast cancer lead molecule.

Pentafuhalol-B, a Phlorotannin from Brown Algae, Strongly Inhibits the PLK-1 Overexpression in Cancer Cells as Revealed by Computational Analysis.

Polo-like kinase-1 (PLK-1) is an essential mitotic serine/threonine (Ser/Thr) kinase that belongs to the Polo-like kinase (PLK) family and is overexpressed in non-small cell lung cancer (NSCLC) via promotion of cell division. Therefore, PLK-1 may act as a promising target for the therapeutic cure of various cancers. Although a variety of anti-cancer drugs, both synthetic and naturally occurring, such as volasertib, onvansertib, thymoquinone, and quercetin, are available either alone or in combination with other therapies, they have limited efficacy, especially in the advanced stages of cancer. To the best of our knowledge, no anticancer agent has been reported from marine algae or microorganisms to date. Thus, the aim of the present study is a high-throughput virtual screening of phlorotannins, obtained from edible brown algae, using molecular docking and molecular dynamic simulation analysis. Among these, Pentafuhalol-B (PtB) showed the lowest binding energy (best of triplicate runs) against the target protein PLK-1 as compared to the reference drug volasertib. Further, in MD simulation (best of triplicate runs), the PtB-PLK-1 complex displayed stability in an implicit water system through the formation of strong molecular interactions. Additionally, MMGBSA calculation (best of triplicate runs) was also performed to validate the PtB-PLK-1 complex binding affinities and stability. Moreover, the chemical reactivity of PtB towards the PLK-1 target was also optimised using density functional theory (DFT) calculations, which exhibited a lower HOMO-LUMO energy gap. Overall, these studies suggest that PtB binds strongly within the pocket sites of PLK-1 through the formation of a stable complex, and also shows higher chemical reactivity than the reference drug volasertib. The present study demonstrated the inhibitory nature of PtB against the PLK-1 protein, establishing its potential usefulness as a small molecule inhibitor for the treatment of different types of cancer.

An ultrasound assisted, ionic liquid-molecular iodine synergy driven efficient green synthesis of pyrrolobenzodiazepine-triazole hybrids as potential anticancer agents.

Herein, we report an efficient and eco-friendly, ultrasound assisted synthetic strategy for the construction of diversified pyrrolobenzodiazepine-triazole hybrids, which are potentially pharmaceutically important scaffolds, via a domino reaction involving intermolecular electrophilic substitution followed by intramolecular Huisgen 1,3-dipolar azide-alkyne cycloaddition. The USP of the reported protocol is the use of benign and inexpensive, recyclable molecular iodine-ionic liquid synergistic catalytic system cum reaction media for achieving the synthesis. The other salient features of this method are the use of mild reaction conditions, high yield and atom economy, operational simplicity, broad substrate scope and easy workup and purification. All the synthesized compounds were evaluated for in vitro anti-proliferative activity against various cancer cell lines. From among the synthesized title compounds, 9,9-dimethyl-8-phenyl-9H-benzo [b]pyrrolo [1,2-d][1,2,3]triazolo[5,1-g][1,4]diazepine (7) was found most to be the most active compound exhibiting IC50 value of 6.60, 5.45, 7.85, 11.21, 12.24, 10.12, and 11.32 µM against MCF-7, MDA-MB-231, HeLa, SKOV-3, A549, HCT-116 and DLD-1 cell lines, respectively. Further the compounds were found to be non-toxic against normal human embryonic kidney (HEK-293) cell line.

Oxygen- and Sulphur-Containing Heterocyclic Compounds as Potential Anticancer Agents.

Oxygen- and sulphur-based heterocycles form the core structure of many biologically active molecules as well as U.S. FDA-approved drugs. Moreover, they possess broad range of biological activities, viz. anticancer, antiinflammatory, antioxidant, antitumour, antibacterial, antiviral, antidiabetic, anticonvulsant, anti-tubercular, analgesic, anti-leishmanial, antimalarial, antifungal, and anti-histaminic, Hence, O- and S-based heterocycles are gaining more attention in recent years on the road to the discovery of innovative anticancer drugs after the extensive investigation of nitrogen-based heterocycles as anticancer agents. Several attempts have been made to synthesize fused oxygen- and sulphur-based heterocyclic derivatives as joining one heterocyclic moiety with another may lead to improvement in the biological profile of a molecule. Humans have been cursed with cancer since long time. Despite the development of several heterocyclic anticancer medications such as 5-fluorouracil, doxorubicin, methotrexate, and daunorubicin, cure of cancer is difficult. Hence, researchers are trying to synthesize new fused/spiro heterocyclic molecules to discover novel anticancer drugs which may show promising anticancer effects with fewer side effects. Furthermore, fused heterocycles behave as DNA intercalating agents which have the ability to interact with DNA, leading to cell death thereby exerting anticancer effect. This review article highlights the synthesis and anticancer potentiality of oxygen- and sulphur-containing heterocyclic compounds covering the period from 2011 to 2021.

Design and Development of Triazole Derivatives as Prospective Anticancer Agents: A Review.

BACKGROUND: In recent years, there has been a crucial need for the design and development of novel anticancer drugs that can lessen the serious health problems and unwanted side effects associated with currently used anticancer drugs. The triazole nucleus is well-recognized to possess numerous pharmacological activities, including anticancer, as revealed by various investigations on anticancer drugs and the latest research findings. OBJECTIVE: The aim of this review article is to summarise the anticancer potential of 1, 2, 3-triazole, 1, 2, 4-triazole and heterocycle-fused triazole derivatives against several human cancer cell lines, compiling research articles published between 2010 and 2021. METHODS: Data were collected from PubMed, Google scholar and Research Gate using keywords "anticancer activity of 1, 2, 3-triazole derivatives", "anticancer activity of 1, 2, 4-triazole derivatives" and "anticancer activity of heterocycle- fused triazole derivatives" and reviewed comprehensively. RESULTS: This review examines the anticancer potential of 1,2,3-triazole coupledoleanolic acid/dithiocarbamate/ pyrido[ 2,3-d] pyrimidine derivatives, 1,2,3-triazole linked pyrimidine/1,4-naphthoquinone hybrids, and 1,2,4-triazole substituted methanone derivatives, acridine-based 1,2,4-triazole derivatives, 1,2,4-thiadiazol coupled with 1,2,4- triazole and 5-ene-thiazolo[3,2-b][1,2,4]triazole-6(5H)-one derivatives against several human cancer cell lines. CONCLUSION: This review highlights the key findings in the area of cancer therapy. Triazole derivatives possess anticancer activity against various human cancer cell lines, and hence the triazole core may act as a lead molecule for the synthesis of novel anticancer drugs.

Unmodified household coffee maker assisted extraction and purification of anticancer agents from Dillenia indica fruits.

Bioassay targeted, 80% aqueous ethanol crude extract of the fruits of Dillenia indica Linn, using the unmodified household coffee maker, afforded five compounds, namely betulinic acid (1), rhamnazin (2), dillenetin (3), luteolin-7-O-ß-D-glucoside (4) and hypolaetin-8-O-ß-D-glucoside (5). The crude extract, fractions and purified compounds were tested against MDA MB-231, A549 and HeLa cancer cell lines by MTT assay, using betulinic acid 1, as a positive control. Compound 3 showed the best activity against A549 (IC50 = 26.60 ± 2.5 µM) and HeLa cancer cell lines (IC50 =19.35 ± 0.9 µM), whereas compound 5 was found to show the best activity against MDA MB-231 (IC50 = 34.62 ± 5.2µM) cancer cell line. These highly potent anticancer compounds obtained from the fruits of D. indica may be suitable for herbal drug development and formulations.

Phenanthridine derivatives as promising new anticancer agents: synthesis, biological evaluation and binding studies.

Aim: Phenanthridines are an essential class of nitrogenous heterocycles with extensive applications in medicinal chemistry. The development of efficient and eco-friendly methods for the preparation of chirally pure dihydropyrrolo[1,2-f]phenanthridines (5a-h), and their in vitro evaluation and modeling studies as potential anticancer, antioxidant and DNA cleavage agents is reported. Methodology & results: Compounds 5a-h were prepared through a facile one-pot synthesis and characterized by infrared, high resolution mass spectrometry, 1H and 13C nuclear magnetic resonance. The molecules were subjected to virtual screening and docking analysis against selected human molecular targets. Compound 5g displayed good binding properties as well as significant anticancer and DNA cleavage activity. Conclusion: Compound 5g has been identified as a potential lead candidate for further testing against additional cancer cell lines and animal models in future.

Recent advances in the targeting of human DNA ligase I as a potential new strategy for cancer treatment.

The emergence of drug resistance, coupled with the issue of low tumor selectivity and toxicity is a major pitfall in cancer chemotherapy. It has necessitated the urgent need for the discovery of less toxic and more potent new anti-cancer pharmaceuticals, which target the interactive mechanisms involved in division and metastasis of cancer cells. Human DNA ligase I (hligI) plays an important role in DNA replication by linking Okazaki fragments on the lagging strand of DNA, and also participates in DNA damage repair processes. Dysregulation of the functioning of such ligases can severely impact DNA replication and repair pathways events that are generally targeted in cancer treatment. Although, several human DNA ligase inhibitors have been reported in the literature but unfortunately not a single inhibitor is currently being used in cancer chemotherapy. Results of pre-clinical studies also support the fact that human DNA ligases are an attractive target for the development of new anticancer agents which work by the selective inhibition of rapidly proliferating cancer cells. In this manuscript, we discuss, in brief, the structure, synthesis, structure-activity-relationship (SAR) and anticancer activity of recently reported hLigI inhibitors.

Dithiolethiones: a privileged pharmacophore for anticancer therapy and chemoprevention.

Dithiolethiones are five-membered sulfur-containing cyclic scaffolds that exhibit antioxidative, anti-inflammatory, antithrombic and chemotherapeutic activities. Dithiolethiones display the chemopreventive and cytoprotective effects by activating the antioxidant response element and mounting the transcription of cytoprotective phase II enzymatic machinery. In addition, several classes of dithiolethiones efficiently modulate the activities of proteins that play crucial roles in normal and cancer cells, including glutathione S-transferase, cyclooxygenases and master regulator NF-κB. The present paper summarizes synthetic aspects, pharmacological potentials and biological attributes of dithiolethiones and its derivatives. Additionally, this review concludes with a discussion on how the current state-of-the-art technologies may help in defining a structure-activity relationship of dithiolethiones, thereby facilitating the design and synthesis of potent drug candidates.

Cosmetic evaluation of surgical scars after external dacryocystorhinostomy.

AIM: To evaluate the surgical scars of external dacryocystorhinostomy (DCR) cosmetically. METHODS: Totally 50 consecutive cases of primary acquired nasolacrimal duct obstruction (PANDO) were included in the study. Surgical scars were assessed by the patients and two independent observers at 2, 6 and 12wk postoperatively on the basis of visibility of the scars and still photographs respectively and were graded from 0-3. Kappa test was utilised to check the agreement of scar grading between the two observers. Wilcoxan signed ranks test was used to analyse the improvement of scar grading. RESULTS: Thirty-four (68%) patients graded their incision site as very visible (grade 3) at 2wk. At 6 and 12wk, incision site was observed as grade 3 by 7 (14%) and 1 (2%) patients respectively. Photographic evaluation of patients by 2 observers showed an average score of 2.75, 1.94 and 0.94 at 2, 6 and 12wk respectively. Change in scar grading from grade 3 to grade 0 in consecutive follow-up (2, 6 and 12wk) was found to be highly significant both for the patient as well for the observers (P<0.0001). CONCLUSION: The external DCR is a highly effective and safe procedure and in view of low percentage of cases who complained of marked scarring in the present study, thus scarring should not be the main ground for deciding the approach to DCR surgery, even in young cosmetically conscious patients.

Fluorescence in situ hybridization of three oncogenes on a leiomyoma.

Using fluorescence in situ hybridization technique, expression of three oncogenes, C-myc, RARa, and cyclin-D was tested on a uterine leiomyoma. C-myc and RARa were amplified in approximately 30% and 90% of the cells, respectively. Numerous small signals of C-myc were indicative of the presence of double minutes. Amplification of RARa is being reported for the first time in a leiomyoma. Cyclin-D was normal in diploid cells while it was highly amplified in polyploid cells. Low levels of amplified C-myc and cyclin-D cells seem to be the reason for this tumor to be benign, while RARa could not be effective without the association of some other gene such as PML. Information presented here are significant toward developing new curative strategies such as gene-specific drugs and molecular manipulation to stop the activity of cancer gene. Further study may elucidate that how fibroids grow and maintain their rare benign nature.

Clonal Variation within an Adenocarcinoma of the Endometrium Cultured in Different Substrates and Media.

An adenocarcinoma of the endometrium was cultured separately in four different combinations of two substrates (normal tissue culture plastic and PrimariaTM) and two media (RPMI-1640 and serum free LHC-9). Our study substantiates our earlier view that no specific combination of substrate and media is superior to any other; rather, it is dependent upon the compatibility of a clone with that specific substrate and media combination.