Anticancer Activity Research Articles

Synthesis of new pyridine based ONNO type schiff bases and Cd(II) complexes, investigation of structural, electronic and anti-cancer properties as computationally and experimentally

Pyridine based Schiff bases and their Cd(II) complexes were synthesized and characterized by spectral techniques which are ATR-IR, 1H NMR, 13C NMR, LC/QTOF-MS, and Single Crystal XRD. Structural properties and geometric parameters of these compounds were investigated both experimental and computational analyses. Electronic properties of Schiff bases were investigated by Hirshfeld surface analyses and molecular electrostatic potential (MEP) map calculations. All experimentally obtained data were supported by computational chemistry methods. B3LYP/6–31G(d) level was used for synthesized Schiff bases while B3LYP/6–31G(d)(LANL2DZ) level was used for Cd(II) complexes. Cell viability assays were performed to determine anticancer properties of related compounds against breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (HT-29), and gastric carcinoma (SNU-16) cell lines. It was found that anticancer activity increased with complexation. The synthesized molecules were found to be more effective against HT-29. Furthermore, molecular docking calculations for each compounds were done against histone deacetylase 1 (HDAC1) due to the fact that expression level of HDAC1 is acceptable range.

Revealing the molecular mechanism of baohuoside I for the treatment of breast cancer based on network pharmacology and molecular docking

Ethnopharmacological relevanceIn Traditional Chinese Medicine (TCM), there are many prescriptions for treating breast cancer (BC) that utilize the herb Epimedium brevicornum Maxim, which warms and replenishes kidney yang. Baohuoside I (BI) is a flavonoid compound found in Epimedium brevicornum Maxim. As a single glycoside, it is not easily hydrolyzed in the intestine and is typically absorbed as a precursor. As a natural product with potential anti-cancer properties, studies have shown that BI possesses anti-cancer activity and can inhibit the invasion and migration of BC cells. However, its underlying mechanisms remain unclear, thus further research is needed to validate its modern mechanisms for traditional uses. Aim of the studyThis study aimed to explore the regulatory mechanism of BI in the signaling pathways of BC cells through network pharmacology (NP), molecular docking (MD) techniques and cellular experiments. MethodsPotential targets were predicted using public databases, and a protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Key signaling pathways were validated through MD techniques, cellular experiments, RNA interference and Western blot (WB) analysis. ResultsTreatment-associated targets included SRC, MAPK1, HSP90AA1, PIK3CA, TP53, AKT1, and EGFR. GO enrichment, KEGG enrichment analyses, and MD results indicated that BI exerts its anti-breast cancer effects by inhibiting the tyrosine kinase activity of EGFR, as well as through downstream MAPK signaling pathway and PI3K-Akt signaling pathway pathways. In vitro experiments confirmed that BI primarily induce cell apoptosis through the EGFR-mediated MAPK signaling pathway and PI3K-Akt signaling pathway. ConclusionBI can inhibit EGFR activation and promote BC cell apoptosis through the MAPK signaling pathway and PI3K-Akt signaling pathway, thereby exerting therapeutic effects on BC. This study not only provides experimental evidence for the accuracy of NP but also offers an effective approach for rational utilization of Baohuoside I-like flavonoid compounds as anti-breast cancer drugs.

RETRACTED: El-Far et al. Nanonutraceuticals: Anti-Cancer Activity and Improved Safety of Chemotherapy by Costunolide and Its Nanoformulation against Colon and Breast Cancer. Biomedicines 2021, 9, 990.

The journal retracts the article, "Nanonutraceuticals: Anti-Cancer Activity and Improved Safety of Chemotherapy by Costunolide and Its Nanoformulation against Colon and Breast Cancer" [...].

Chitosan Encapsulated Silver Nanoparticles by Brassica oleracea leaf Extract: An in-vitro Antioxidant, Antimicrobial and Anticancer Activity on Breast Cancer MCF-7

Chitosan Encapsulated Silver Nanoparticles by Brassica oleracea leaf Extract: An in-vitro Antioxidant, Antimicrobial and Anticancer Activity on Breast Cancer MCF-7

Urea and Thiourea Derivatives of Salinomycin as Agents Targeting Malignant Colon Cancer Cells.

Since it was discovered that a natural polyether ionophore called salinomycin (SAL) selectively inhibits human cancer cells, the scientific world has been paying special attention to this compound. It has been studied for nearly 15 years. Thus, a very interesting research direction is the chemical modification of SAL structure, which could give more biologically active agents. We evaluated the anticancer activity of (thio)urea analogues class of C20-epi-aminosalinomycin (compound 3b). The studies covered the generation of reactive oxygen species (ROS), proapoptotic activity, cytotoxic activity, and lipid peroxidation in vitro. Thioureas 5a‒5d showed antiproliferative activity against selected human colon cancer cell lines greater than that of chemically unmodified SAL, with a 2~10-fold higher potency towards a metastatic variant of colon cancer cells (SW620). Mechanistically, SAL derivatives showed pro-apoptotic activity in primary colon cancer cells and induced the production of reactive oxygen species (ROS) in these cells. In SW620 cells, SAL derivatives increased lipid peroxidation with a weak effect on apoptosis and low ROS formation with cytotoxic effects followed by cytostatic ones, suggesting different modes of action of the compounds against primary and metastatic colon cancer cells. The results of this study suggested that urea and thiourea derivatives of SAL provide promising leads for the rational development of new anticancer active agents.

Identification of 3-methyl-1-(3-methylpyridin-2-yl)-1H-pyrazol-5-ol as promising neuroprotective agent

Pyrazolol derivatives are gaining significant attention for their diverse pharmacological effects, such as analgesic, anti-inflammatory, antioxidant, and anticancer activities. In this study, 20 pyrazolol derivatives were designed and synthesized to develop an anti-ischemic stroke formulation with free radical scavenging activity. Most of these synthesized compounds demonstrated antioxidant capabilities in DPPH, ABTS radical scavenging, and ORACFL assays. The methyl-substituted compound Y12, in particular, showed exceptional antioxidant capacity. Additionally, these compounds showed excellent neurocytoprotective effects in the SH-SY5Y cell injury model subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Notably, Y12 exhibited significant metal chelating activity with Cu2+. In vivo studies confirmed that compound Y12 has neuroprotective effects and can significantly reduce the infarct area in a mouse model of focal cerebral ischemia induced by transient middle cerebral artery occlusion (tMCAO).

In-silico and In-vitro Investigation of Flavonoids and Alkaloids from Artocarpus heterophyllus, Tinospora cordifolia, and Glycosmis pentaphylla as Potential NF-κB Inhibitors in Oral Cancer.

Oral cancer is a global health concern, particularly because of its aggressive tissue invasion and metastases, holding 16th position on occurrence among all carcinoma worldwide. The aberrated transcription factor NF-κB1 influences development and spread of oral cancer, making it a potential therapeutic target. This study investigated the therapeutic potential of a few natural compounds from Artocarpus heterophyllus, Tinospora cordifolia, and Glycosmis pentaphylla in the treatment of oral cancer. Two FDA-approved drugs (5-fluorouracil, Docetaxel) and 16 natural compounds, including Artocarpin, Artocarpanone, Cycloartocarpin from Artocarpus heterophyllus; Berberine, Hydrastine, Magnoflorine, Palmatine Chloride, Tetrahydropalmatine from Tinospora cordifolia; and 5-Hydroxyarborinine, 5-Hydroxynoracronycine, 1-Hydroxy-3-methoxy-10-methyl-9-acridone, Des-N-methylacronycine, Des-N-methylnoracronycine, Kokusagenine, Noracronycin, Skimmianine from Glycosmis pentaphylla were examined using in-silico techniques. Among the 16 natural compounds studied, Hydrastine shown the highest binding energy (-6.87 kcal/mol) against NF-κB1, surpassing all other drugs, including the standards 5-fluorouracil (-4.04 kcal/mol) and docetaxel (-2.4 kcal/mol). Further molecular dynamics simulations and in-vitro experiments verified Hydrastine's exceptional anti-cancer activity. The results of in-vitro were well-aligned with the findings of in-silico, revealing considerable cytotoxicity, apoptosis induction, and cell cycle arrest. The findings revealed natural compounds' potential as safer, more effective alternatives to current cancer therapeutics, opening up new avenues for oral cancer treatment.

Synthesis, characterization and anticancer investigation of some novel 2,5-disubstituted-1,3-thiazol-4-(5H)-ones and 1-substituted-1H-pyrazolo[3,4-d] thiazole derivatives

Fused pyrazoles and 2,5-disubstituted thiazolinone derivatives are attractive molecules for drug design development that are widely recognized as significant biological activity exhibition scaffolds. A considerable number of them were utilized as anti-cancer medications. In this current study, hybrid molecules that exhibited kinase inhibitory activity in addition to anti-tumor properties were synthesized. Our plan was to create a series of disubstituted-1,3-thiazolinone on fused pyrazolo[3,4-d]-thiazole derivatives as efficient anti-cancer drugs with low cytotoxicity and significant biological availability properties using 2-hydroxy acetophenone thiosemicarbazene and ethyl chloroacetate to provide 2-[2-(2-hydroxy phenyl)ethylidene)hydrazinyl]-1,3-thiazole-(5H)-one (3) as the essential precursor to heterocyclization processes. Compounds (3–8) were prepared and identified using infrared, 1H, and 13C NMR spectral data. These synthesized compounds were evaluated for their in vitro cytotoxic activity against the two cancer cell lines (MCF-7 breast cancer and HepG2 liver cancer). The preliminary screening of their compounds for their anti-cancer activity revealed that compound (6) possessed the highest anti-cancer activity. It's interesting to note that these substances, when compared to the reference medicines Erlotinib and Lapatinib, respectively, significantly caused apoptosis in the HepG2 and MCF-7 cell lines using flow cytometry analysis, suggesting potentially high therapeutic ratios.

Novel Bis-1,2,3-triazole-thiazolidinone hybrid as anticancer agents that induce apoptosis and molecular modeling study.

Aim: A series of (R)-Carvone-based 1,2,3-triazole-thiazolidinone 17a-h hybrids were synthesized and characterized by spectroscopic techniques NMR and HRMS. The chemical reactivity and the stability parameters were observed via DFT.Method/results: The objective was to evaluate the anticancer activity of the synthesized compounds against cancer cell lines. The mechanism of action by which the 17b and 17g exert their effect suggested that they may induce apoptosis through activation of caspase-3/7. This effect was observed against the most important NIMA-related kinases via Docking investigation. The designed compounds were identified as the best inhibitors of the NEK family via the inactivation of the caspase-3. The Docking results were supported by Dynamics where the binding energies justified the medicinal importance of the synthesized derivatives.

Sustained Clinical Benefit and Intracranial Activity of Tarlatamab in Previously Treated Small Cell Lung Cancer: DeLLphi-300 Trial Update.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3, has shown durable anticancer activity and manageable safety in previously treated small cell lung cancer (SCLC) in DeLLphi-300 phase I and DeLLphi-301 phase II trials. Here, we report extended follow-up of DeLLphi-300 (median follow-up, 12.1 months [range, 0.2-34.3]) in fully enrolled cohorts treated with tarlatamab ≥10 mg dose administered once every two weeks, once every three weeks, or once on day 1 and once on day 8 of a 21-day cycle (N = 152). Overall, the objective response rate (ORR) was 25.0%; the median duration of response (mDOR) was 11.2 months (95% CI, 6.6 to 22.3), and the median overall survival (mOS) was 17.5 months (95% CI, 11.4 to not estimable [NE]). Among 17 patients receiving 10 mg tarlatamab once every two weeks, the ORR was 35.3%, the mDOR was 14.9 months (95% CI, 3.0 to NE), the mOS was 20.3 months (95% CI, 5.1 to NE), and 29.4% had sustained disease control with time on treatment ≥52 weeks. No new safety signals were identified. In modified Response Assessment in Neuro-Oncology Brain Metastases analyses, CNS tumor shrinkage of ≥30% was observed in 62.5% of patients (10 of 16) who had a baseline CNS lesion of ≥10 mm, including in a subset of patients with tumor shrinkage long after previous brain radiotherapy. In DeLLphi-300 extended follow-up, tarlatamab demonstrated unprecedented survival and potential findings of intracranial activity in previously treated SCLC.

Synthesis of chlorotoxin functionalized metallic nanoparticles and their in vitro evaluation of cytotoxic effects in nervous system cancer cell lines

The treatment of glioblastoma (GB) and neuroblastoma (NB) remains a challenge, as current chemotherapies are plagued with systemic toxicity, drug resistance, and inadequate blood–brain barrier (BBB) penetration. Therefore, novel therapeutic strategies with high specificity and the capacity to bypass the BBB are required. Chlorotoxin (CTX) selectively targets gliomas and neuroectodermal tumors, hence the use of CTX-targeted nanoparticles (NPs) represents a promising therapeutic approach for nervous system (NS) cancers. Bimetallic NPs composed of two metals such as gold-platinum NPs (AuPtNPs) exhibit enhanced anticancer properties compared to single-metal NPs, however their application in studying NS tumors has been relatively limited. CTX-functionalized monometallic gold NPs (CTX-AuNPs) and bimetallic gold-platinum NPs (CTX-AuPtNPs) were synthesized in this study. The NPs were characterized by Ultraviolet-Visible Spectroscopy (UV–vis), Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) and Fourier Transform Infra-Red Spectroscopy (FTIR). Cytotoxicity of NPs was investigated in cancer (U87 and SH-SY5Y) and non-cancer (KMST-6) cells using the water-soluble tetrazolium (WST)-1 assay. The CTX-AuNPs and CTX-AuPtNPs had a core size of ∼5 nm. The CTX-AuPtNPs showed significant anticancer activity in U87 cells possibly due to the synergistic effects of combined metals. Findings obtained from this study demonstrated that CTX can be used to target NS cancers and that bimetallic NPs could be effective in their treatment. More studies are required to investigate the mechanisms of NPs toxicity, and further explore the hyperthermia treatment of NS cancer using the CTX-AuPtNPs.

Anticancer Activity of Vitamin D, Lumisterol and Selected Derivatives against Human Malignant Melanoma Cell Lines.

Despite the recent development of improved methods of treating melanoma such as targeted therapy, immunotherapy or combined treatment, the number of new cases worldwide is increasing. It is well known that active metabolites of vitamin D3 and lumisterol (L3) exert photoprotective and antiproliferative effects on the skin, while UV radiation is a major environmental risk factor for melanoma. Thus, many natural metabolites and synthetic analogs of steroidal and secosteroidal molecules have been tested on various cancer cells and in animal models. In this study, we tested the anti-melanoma properties of several natural derivatives of vitamin D3 and L3 in comparison to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). A significant decrease in melanoma cell proliferation and cell mobility was observed for selected derivatives, with (25R)-27-hydroxyL3 showing the highest potency (lowest IC50) in A375 cells but lower potency in SK-MEL-28 cells, whereas the parent L3 failed to inhibit proliferation. The efficacy (% inhibition) by 1,24,25(OH)3D3 and 1,25(OH)2D3 were similar in both cell types. 1,25(OH)2D3 showed higher potency than 1,24,25(OH)3D3 in SK-MEL-28 cells, but lower potency in A375 cells for the inhibition of proliferation. As for 1,25(OH)2D3, but not the other derivatives tested, treatment of melanoma cells with 1,24,25(OH)3D3 markedly increased the expression of CYP24A1, enhanced translocation of the vitamin D receptor (VDR) from the cytoplasm to the nucleus and also decreased the expression of the proliferation marker Ki67. The effects of the other compounds tested were weaker and occurred only under certain conditions. Our data indicate that 1,24,25(OH)3D3, which has undergone the first step in 1,25(OH)2D3 inactivation by being hydroxylated at C24, still shows anti-melanoma properties, displaying higher potency than 1,25(OH)2D3 in SK-MEL-28 cells. Furthermore, hydroxylation increases the potency of some of the lumisterol hydroxy-derivatives, as in contrast to L3, (25R)-27(OH)L3 effectively inhibits proliferation and migration of the human malignant melanoma cell line A375.

Natural Products-Based Anticancer Agents: Synthesis and Anticancer Activities of Funtumine Amide/sulfonamide Derivatives.

Funtumine is a pregnene-type steroidal alkaloid exhibiting moderate anticancer activity. To discovernovel natural product-based anticancer drugs, a series of novel funtumine amide/sulfonamide derivatives were papered and identified using spectroscopic techniques. Additionally, the structures of compounds 2j, 3a, and 4kwere further confirmed through X-ray diffraction analysis. Biological activity experiments conducted against three cancer cell lines revealed that several of the synthesized compounds demonstrated inhibition activities comparable to or exceeding those of the commercial anticancer agent, 5-Fluorouracil. Especially compound 4idemonstrated a notably strong growth inhibitory effect on HePG2 (IC50= 14.89 μM) and HCT116 (IC50= 15.67 μM) cell lines, while exhibiting minimal cytotoxicity towards human normal BEAS-2B cells. Preliminary structure-activity relationships (SARs) analysis indicated that the conversion of the carbonyl group at the C-20 position of funtumine to a hydroxyl group could yield more potent compounds.

Cucurbitacin-E; Curvularia lunata Secondary Metabolite as a BRCA 1 and 2 Regulator in Mice Associated Breast Cancer

Background: Cucurbitacin-induced apoptosis and inhibition of cell growth can render several cancers ineffective. The microbial transformation of cucurbitacin-E-glucoside to cucurbitacin- E was carried out by Curvularia lunata (NRRL 2178). Moreover, in vitro anticancer activity against the MCF-7 cell line as well as in vivo anticancer activity against dimethylbenz (a) anthracene (DMBA)-induced breast cancer in mice using cucurbitacin-E was evaluated. Methods: The cucurbitacin-E-glucoside was biotransformed by Curvularia lunata to cucurbitacin- E, and the isolated compound was tested in vitro against the MCF-7 cell line, and its IC50 was calculated. LD50 of cucurbitacin-E was estimated in mice, and its protective activity against DMBA-induced cancer in mice was studied. Breast cancer induction was done by a single-dose subcutaneous administration of DMBA (50 mg). Plasma ALT, AST, ALP, and LDH, as well as GSH, SOD, GPx, MDA, TNF-α, IL-6, and tumor suppressor P53 assays, were used to assess cucurbitacin- E's capacity to protect the liver and breast against DMBA-induced toxicity. Moreover, by assessing the gene expression of tumor suppressor genes (BRCA 1 and 2) and conducting histopathological analysis, the suppressive effect of cucurbitacin-E was examined. Results: The IC50 value of cucurbitacin-E against MCF-7 cell lines equals 72.15 ± 0.64 μg/ml. LD50 of cucurbitacin-E given orally in adult mice is equal to 1200 mg/kg b.w. The levels of plasma ALT, AST, ALP, and LDH were decreased significantly in DMBA-treated mice when administered with cucurbitacin-E at 1/50 LD50 (24 mg/kg/b.w.) and 1/20 LD50 (60 mg/kg/b.w.). In breast tissue, the levels of GSH, SOD, GPx, and P53 were significantly increased, as were decreased levels of TNF-α, IL-6, P53, and MDA. Conversely, there was a downregulation in the mRNA expression levels of BRCA1 and BRCA2. The histopathological analysis revealed that cucurbitacin-E management improved the tissue architecture of breast tumors. Conclusions: These findings demonstrate the ability of cucurbitacin-E to inhibit cancer cells in the rat breast by controlling oxidative stress and inflammatory biomarkers, as well as downregulating the mRNA expression levels of BRCA1 and BRCA2.

Multicomponent Cyanation of 2‐Amino‐3‐cyano‐4H‐chromenes in Aqueous Media

Chromenes represent a pivotal molecular structure found in a diverse range of biologically active compounds. Specifically, derivatives of 2‐amino‐3‐cyano‐4H‐chromene have demonstrated pharmacological applications, displaying potential antioxidant and anticancer activities. This has heightened interest in the exploration of new and more efficient methods for their synthesis. In recent years, few examples have emerged, focusing on the organocatalytic and enantioselective synthesis of 2‐amino‐3‐cyano‐4H‐chromene derivatives, although the overall number of works to date is limited. In this study, we present the results of the synthesis of 2‐amino‐4H‐chromen‐3,4‐dicarbonitriles through a Michael addition of cyanide to 2‐iminochromenes. To achieve this, we utilized a mild source of cyanide (acetone cyanohydrin), green solvents and catalytic conditions at room temperature, via a multicomponent approach. Furthermore, we initiated the enantioselective study of this process using chiral organocatalysts obtaining promising preliminary results.

Cruciferous Plant Extracts, Their Isothyocianate or Indol Derivatives, and Their Effect on Cellular Viability of Breast Cancer Cell Lines.

Brassicaceaes are rich in glucosinolates (GSL), whose derivatives, the isothyocianates sulforaphane (SFN), iberine (IB), or indole derivatives as indole-3-carbinol (I3C), have anticancer activities. We evaluated the effects of a broccoli sprout (Brassica oleracea var italica) and red cabbage (B. oleracea L. var capitata f. rubra) extracts and their GSL derivatives on breast cancer cells. Broccoli sprout aqueous extract (BSE) and red cabbage aqueous (RCA) or ethanolic (RCE) extracts were high in SFN, IB, and/or I3C. BSE and RCA decreased proliferation at doses of 2.5-5 mg/mL but induced proliferation at lower doses. RCE decreased proliferation starting at 10 µg/mL with selectivity toward cancer cells. SFN, IB, or I3C alone or in combination did not decrease proliferation similarly, suggesting synergistic effects with other phytochemicals in the extract. RCE showed selectivity toward breast cancer cells, but the effect of the individual metabolites or their combination did not reduce proliferation to the same extent. It will be important to determine the combination responsible for this effect to characterize their use for breast cancer treatment.

O-Allyloxy chalcone derivatives: design, synthesis, anticancer activity, network pharmacology and molecular docking

O-Allyloxy chalcone derivatives: design, synthesis, anticancer activity, network pharmacology and molecular docking

Eco-friendly synthesis of curcumin-loaded ZnO nanoparticles encapsulated in Pluronic F-127: Implications for bacterial and breast cancer therapies

The development of a nanomaterials production process that is both economical and environmentally friendly is a result of the growing importance placed on people’s health. The Zinc oxide (ZnO)-Pluronic F127 (PF127)-Curcumin (CUR) nanoparticles (NPs) were synthesized through a green method using Senna auriculata flower extracts. These NPs were characterized using a variety of techniques, such as ultraviolet–visible spectroscopy (UV), Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (FESEM), Energy Dispersive X-ray analysis (EDAX), X-ray diffraction (XRD), photoluminescence (PL), and dynamic light scattering (DLS). From the XRD studies, synthesized ZnO-PF127-CUR NPs exhibit a wurtzite hexagonal crystal structure. The antimicrobial activity of ZnO-PF127-CUR NPs and Amoxicillin was tested against Staphylococcus aureus, Klebsiella pneumoniae, Shigella dysenteriae, Staphylococcus pneumoniae, Bacillus subtilis, proteus vulgaris, and candida albicans, respectively. The anticancer activity of ZnO-PF127-CUR NPs was tested against human breast cancer cell line (MDA-MB-237), and ZnO-PF127-CUR exhibits potential anticancer activity. These results support using ZnO-PF127-CUR NPs in healthcare manufacturing environments to improve human health.

Recent Advances in Phenazine Natural Products: Chemical Structures and Biological Activities.

Phenazine natural products are a class of colored nitrogen-containing heterocycles produced by various microorganisms mainly originating from marine and terrestrial sources. The tricyclic ring molecules show various chemical structures and the decorating groups dedicate extensive pharmacological activities, including antimicrobial, anticancer, antiparasitic, anti-inflammatory, and insecticidal. These secondary metabolites provide natural materials for screening and developing medicinal compounds in the field of medicine and agriculture due to biological activities. The review presents a systematic summary of the literature on natural phenazines in the past decade, including over 150 compounds, such as hydroxylated, O-methylated, N-methylated, N-oxide, terpenoid, halogenated, glycosylated phenazines, saphenic acid derivatives, and other phenazine derivatives, along with their characterized antimicrobial and anticancer activities. This review may provide guidance for the investigation of phenazines in the future.

Integrated Transcriptomics and Metabolomics Studies Reveal Steroid Biosynthesis Pathway and BCL2 Inhibitory Diazo-Progesterone of Drimia indica for Conservation and Sustainable Utilization.

This study is the first report on the sequence of the transcriptome of Drimia indica, a non-model plant with medicinal properties found in a forest tribal belt, using the Illumina NovaSeq platform. The primary objectives of this study were to elucidate the gene expression profiles in different tissues, identify key regulatory genes and pathways involved in secondary metabolite biosynthesis, and explore the plant's potential pharmacological properties. The study generated 670087 unigenes from both leaves and roots and identified putative homologs of annotated sequences against UniProt/Swiss-Prot and KEGG databases. The functional annotation of the identified unigenes revealed the secondary metabolite biosynthetic process as the most prominent pathway, with gene enrichment analysis predominantly accounting for secondary metabolite pathways, such as terpenoid, steroid, flavonoid, alkaloid, selenocompound, and cortisol synthesis. The study also identified regulatory genes NAC, Bhlh, WRKY, and C2H2 on the transcriptome dataset. The functionally annotated unigenes suggested phytocompounds in Drimia indica to have multi-potent properties, such as anti-cancer, anti-inflammatory, and anti-diabetic activities, which has been further validated by GC-MS-based metabolite profiling. Notably, we have identified two novel molecules, di-azo progesterone and 4H-pyran-4-one 2,3-dihydro-3,5-dihydroxy- 6-methyl, with potential BCL2 inhibitory anticancer properties, supported by stable binding interactions observed in molecular docking and dynamics simulations. Additionally, an abundance of mono-nucleotide SSR markers has been identified, useful for genetic diversity studies. This study provides a foundational understanding of the molecular mechanisms in Drimia indica, highlighting its potential as a source for novel therapeutic agents and contributing valuable insights for future pharmacological and agricultural applications. However, further in vivo studies are warranted to confirm these findings and validate their pharmacological efficacy and therapeutic potential. The SSR markers identified also offer valuable tools for molecular genetics, plant breeding, and sustainable drug development.