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Item Meso-substitution controlled synthesis of bodipy–dpm conjugates: a pathway to tailored photophysical properties(2026) Roy, Aniruddha; Arora, Pankaj; Grover, NitikaWe show that the electronic nature of the meso-aryl substituent in 1,3,5,7-tetramethyl BODIPYs governs the reactivity of the 1,7-methyl (α-methyl) groups toward the Knoevenagel condensation. Reaction of pyrrole-2-aldehyde with electron-deficient 1,3,5,7-tetramethyl-meso-pentafluorophenyl and 1,3,5,7-tetramethyl-meso-4-nitrophenyl BODIPYs yields double condensation at the 1,7-methyl positions to give the corresponding bis(pyrrole) derivatives, whereas the electron-rich meso-tolyl analogue selectively undergoes single condensation at only one of the α-methyl groups under identical conditions. This substituent-dependent divergence extends to reactions with 1,9-diformyl-meso-aryl dipyrromethanes, enabling access to structurally distinct BODIPY–DPM conjugates. Reaction of 1,9-diformyl-DPM with meso-tolyl BODIPY selectively yields acyclic monosubstituted BODIPY–DPM conjugates, whereas the higher reactivity of meso-pentafluorophenyl BODIPY enables condensation between both 1,7-methyl groups and the two aldehyde functionalities of the diformyl-DPM scaffold, affording cyclic, porphyrin-like BODIPY–DPM frameworks. Notably, meso-pentafluorophenyl BODIPYs also undergo nucleophilic aromatic substitution of the para-fluorine atom by piperidine under the condensation conditions, as confirmed unambiguously by single-crystal X-ray diffraction. The resulting BODIPY–DPM and BODIPY–pyrrole conjugates exhibit pronounced bathochromic shifts (90–180 nm relative to parent BODIPYs), deep-red to near-infrared absorption (~670 nm) and emission (~750 nm), enlarged Stokes shifts, and strong intramolecular charge-transfer character. These features translate into efficient heavy-atom-free triplet formation, with singlet-oxygen quantum yields reaching up to 0.45. A representative conjugate (10) exhibits potent photodynamic activity in B16F10 melanoma cells with minimal dark toxicity (IC₅₀ = 0.95 μM). TD-DFT analysis indicates that excited-state twisting reduces ΔEST, thereby facilitating heavy-atom-independent intersystem crossing. Collectively, these results establish a robust molecular design framework for next-generation heavy-atom-free photosensitizers.Item Shedding light on photo-redox catalysis of NIR iridium (iii) complex for high photocytotoxicity against Cis-platin resistant ovarian cancer in 3d tumor spheroids(RSC, 2025-12) Laskar, Inamur Rahaman; Roy, AniruddhaThe clinical translation of photodynamic therapy (PDT) is often hindered by the lack of photosensitizers (PSs) that achieve potent cytotoxicity at clinically relevant concentrations. This limitation stems from an incomplete understanding of photochemical mechanisms underlying PDT efficacy. Here, we report RM2, a near-infrared Ir(III)-based PS with a high molar absorption coefficient (17,700 M-1 cm-1 at the excitation wavelength), a key feature for attaining low IC50 values. Upon irradiation, RM2 undergoes two distinct single-electron transfer (SET) pathways: catalytic oxidation of NADH with a turnover frequency (TOF) of 690 h-1, and Type-I ROS generation (O₂•⁻ and H2O2), confirmed by EPR spectroscopy and H2O2 detection assays. In addition, RM2 displays a triplet state energy of 37.68 kcal mol-1 (1.63 eV, 762 nm) with a 5 µs lifetime, enabling efficient energy transfer to 3O2 and a singlet oxygen quantum yield (ϕΔ) of 0.75 in cell-free media. Encapsulation of RM2 in DSPE-mPEG2000 nanoparticles further amplified its activity, enhancing photocytotoxicity by 8.3-fold and achieving an IC50 of 60 nM against ovarian cancer cells. Remarkably, RM2 NPs retained this potency in cisplatin-resistant ID8 cells (IC50 = 60 nM), whereas cisplatin itself showed drastically reduced efficacy (IC50 = 10.46 µM in wild-type and 30.41 µM in resistant cells). Additionally, RM2 NPs exhibited pronounced efficacy against 3D ovarian tumor spheroid models, underscoring their translational potential. These results establish RM2 as a multifunctional photosensitizer, in which the synergy of long-lived triplet energy and favorable redox potentials enables diverse photochemical mechanisms, encompassing NADH oxidation and both Type-I and Type-II ROS generation. This multifaceted mechanism of action offers a powerful strategy to overcome hypoxia and drug resistance, significantly advancing the potential of PDT for effective cancer therapy.Item Development of gene expression inhibitors for the treatment of cutaneous carcinomas(Taylor & Francis, 2025-07) Roy, Aniruddha; Singhvi, GautamCutaneous carcinoma is one of the most common cancers worldwide, with rising incidence and mortality rates, especially among white Caucasians. It primarily includes non-melanoma skin cancer (NMSC) and melanoma skin cancer (MSC), which together account for over 90% of all skin cancers. The main cause is the abnormal proliferation of skin cells due to genetic mutations and environmental damage [Citation1]. Basal cell carcinoma (BCC) arises from mutations in the Ptch1 tumor suppressor gene caused by UV-radiations, leading to dysregulated hedgehog signaling, while Squamous cell Carcinoma (SCC), which originates in keratinocytes, is driven by TP53 mutations and epigenetic changes. In melanoma, mutations in genes like B-Raf proto-oncogene, serine/threonine kinase (BRAF), Neuroblastoma RAS Viral Oncogene Homolog (NRAS), Neurofibromin 1 (NF1), or proto-oncogene receptor tyrosine kinase (KIT) activate the MAPK pathway, leading to cellular proliferation and invasion. Traditional treatments, such as surgery, chemotherapy, and immunotherapies, face challenges like resistance, side effects, and don’t address widespread epigenetic alterations that activate oncogenes and silence tumor suppressors, emphasizing the need for targeted genetic therapies to inhibit skin cancer growth [Citation2]. Several gene expression inhibitors are being explored for cutaneous carcinomas, such as DNMT inhibitors (guadecitabine and decitabine, etc), which reverses abnormal DNA methylation to reactivate tumor suppressor genes, while EZH2 inhibitors (CPI-1205) block H3K27 trimethylation to prevent oncogenic gene silencing. HDAC inhibitors (entinostat, mocetinostat, and panobinostat), enhance histone acetylation to promote tumor suppressor expression and improve immune responses, and siRNA-based therapies (STP705 and c-Myc siRNA, etc) or antisense oligonucleotides targeting lncRNAs like MALAT1 and TINCR directly silence cancer-promoting genes and disrupt oncogenic pathways [Citation3]. Therefore, recent investigations focused on the regulation of gene expression and the development of their inhibitors as effective targeted therapeutic strategies for the treatment of cutaneous carcinoma.Item Repurposing of CNS accumulating drugs Gemfibrozil and Doxylamine for enhanced sensitization of glioblastoma cells through modulation of autophagy(Springer Nature, 2025-07) Mukherjee, Sudeshna; Chowdhury, Rajdeep; Majumder, Syamantak; Chowdhury, Shibasish; Roy, AniruddhaGBM is one of the most aggressive malignancies, having the greatest fatality rate and average life years lost. The current standard medicine, temozolomide (TMZ), is ineffective, requiring the development of new treatments. However, identifying and introducing a novel medicine takes time and money. In this context, repurposing FDA-approved drugs can be a novel yet efficient alternative method. Here, we, therefore, investigated the differential expression signatures of genes of patients suffering from GBM from publicly available GEO datasets and constructed a connectivity map. Functional annotation and KEGG pathway analysis showed dysregulated molecular activities and pathways. Based on their gene ontologies, putative key genes and hub genes linked with the disease were identified, and the C-MAP database was scanned for FDA-approved medicinal compounds that could alter hub gene expression or associated pathways. Our in-silico investigation showed that Gemfibrozil (Gem) and Doxylamine (Doxy) might reverse GBM disease patterns by deregulating GBM-related genes. Evaluation of the GBM inhibitory potential of these drugs through in-vitro and three-dimensional spheroid assay showed promising results. These drugs were more cytotoxic than TMZ; however, they synergised with TMZ as well. Interestingly, the cellular homeostatic process autophagy which has been implicated significantly in GBM pathogenesis and therapy resistance, was found to be inhibited by the drugs Gemfibrozil and Doxylamine, signifying their prospective potential. Therefore, in this study, we, for the first time, identify drugs with the ability to cross the blood brain barrier (BBB), with potential cytotoxic effects beyond TMZ, and with autophagy inhibitory potential, which can be further explored for repurposing against GBM.Item Design, synthesis and in vitro evaluation of primaquine and diaminoquinazoline hybrid molecules against the malaria parasite(Wiley, 2025-01) Sundriyal, Sandeep; Roy, AniruddhaIn this study, we built on the known inhibitory potential of diaminoquinazolines (DAQs) against different stages of Plasmodium development and designed a convenient two-step synthesis to combine DAQ with primaquine (PQ) pharmacophore. The PQ-DAQ hybrids displayed potent in vitro activities in the low nanomolar range (IC50 135.20–398.80 nM) against all intra-erythrocytic stages of the drug-sensitive 3D7 strain, with significant potency enhancement compared to PQ alone (IC50 9370 nM). These hybrids were also potent at killing drug-resistant strains (Dd2, Dd2 R539T, IPC4912, CamWT C580Y, and 7G8) in the nanomolar range, with 11 f being the most effective compound (IC50 172.20–396.60 nM). Notably, for the first time, we present evidence that the DAQ-based compound 8 and its hybrids can inhibit β-hematin formation in vitro with potency (IC50 0.90–27.80 μM), suggesting hemozoin formation to be one of the potential targets of this series. Lastly, two hybrids with potent antiplasmodial activity were also found to be safe up to 10 μM against human HepG2 cells, suggesting the possibility of achieving host vs parasite selectivity with this series.Item The power of synergism: a novel drug combination for improved therapy of glioblastoma(Wiley, 2024-05) Roy, AniruddhaOne of the biggest obstacles in treating glioblastoma multiforme (GBM) is the plasticity and adaptability of GBM cells, which renders monotherapy ineffective. Novel drug combinations that target multiple pathways are required to overcome this challenge. In the current study, the PI3K/AKT/mTOR pathway is identified as a crucial component in GBM cell survival using the KEGG database and literature search. Hence, it is hypothesized that a potential synergistic therapy can be achieved by targeting different stages of this pathway by combining disulfiram (DSF) and 7-ethyl-10-hydroxycamptothecin (SN-38). The efficacy of this drug combination is evaluated using 2D and 3D in vitro assays, which exhibited a significant synergism with 5 × 104 times lower IC50 than that of temozolomide (TMZ), the gold-standard drug. The combination treatment increases intracellular ROS (reactive oxygen species) production, and ROS inhibition by using N-Acetyl Cysteine (NAC) reduced the cytotoxicity substantially, indicating that ROS played a crucial role in the synergistic cytotoxicity. The combination treatment inhibited GBM cell proliferation, migration, and stem cell marker expression. Mechanistically, the DSF+SN-38 combination is found to increase p53 expression, inhibit PI3K signaling, and activate caspase 9. Altogether, this study demonstrates that the DSF+SN-38 combination can present a promising therapeutic strategy for treating GBM.Item Synergistic chemo-immunotherapy using ph-responsive nanoparticles in breast cancer treatment: in vitro and in vivo studies(ACS, 2024-10) Roy, AniruddhaRecent research underscores the pivotal role of the heterogeneous multicellular interactome within the tumor microenvironment (TME) in tumor progression and survival. Tumor-associated macrophages (TAMs), among other nonmalignant cells in the TME, promote an immunosuppressive environment, fostering tumor cell survival, proliferation, and resistance. Hence, combining chemotherapy with immunomodulatory agents to transition TAMs to an immunostimulatory phenotype holds immense therapeutic potential. The present study focuses on developing tumor-responsive nanoparticles (NPs) for combined chemo-immunotherapy using resiquimod (RSQ), a TLR 7/8 agonist as an immunomodulator, and paclitaxel (PTX) as chemotherapeutics. A pH-responsive NP known as PHNP, tailored with a star-shaped PLGA conjugated with poly histidine, was engineered to selectively deliver a consistent ratio of PTX and RSQ directly to the tumor site. In vitro studies demonstrate enhanced drug release at pH 6.4, increased penetration in tumor spheroids, and increased cytotoxic efficacy against breast cancer cells. Furthermore, PHNPs activate macrophages for antitumor activity. In vivo studies demonstrated a notable rise in plasma AUC and improved delivery of drugs to the tumor using PHNPs, resulting in enhanced effectiveness against tumor growth in a mouse orthotopic breast cancer model. Notably, PHNP treatment elevated intratumoral ROS and apoptosis levels and inhibited lung metastasis. Overall, this study underscores the potential of the PTX and RSQ combination as a prospective combined chemo-immunotherapeutic modality.Item Targeting tumor microenvironment with photodynamic nanomedicine(Wiley, 2025) Roy, AniruddhaPhotodynamic therapy (PDT) is approved for the treatment of certain cancers and precancer lesions. While early Photosensitizers (PS) have found their way to the clinic, research in the last two decades has led to the development of third-generation PS, including photodynamic nanomedicine for improved tumor delivery and minimal systemic or phototoxicity. In terms of nanoparticle design for PDT, we are witnessing a shift from passive to active delivery for improved outcomes with reduced PS dosage. Tumor microenvironment (TME) comprises of a complex and dynamic landscape with myriad potential targets for photodynamic nanocarriers that are surface-modified with ligands. Herein, we review ways to improvise PDT by actively targeting nanoparticles (NPs) to intracellular organelles such as mitochondria or lysosomes and so forth, overcoming the limitations caused by PDT-induced hypoxia, disrupting the blood vascular networks in tumor tissues—vascular targeted PDT (VTP) and targeting immune cells for photoimmunotherapy. We propose that a synergistic outlook will help to address challenges such as deep-seated tumors, metastasis, or relapse and would lead to robust PDT response in patients.Item Dual-emissive iridium(iii) complex with aggregation-induced emission: mechanistic insights into electron transfer for enhanced hypoxia detection in 3D tumor models(ACS, 2025-01) Roy, Aniruddha; Laskar, Inamur RahamanAccurate oxygen detection and measurement of its concentration is vital in biological and industrial applications, necessitating highly sensitive and reliable sensors. Optical sensors, valued for their real-time monitoring, nondestructive analysis, and exceptional sensitivity, are particularly suited for precise oxygen measurements. Here, we report a dual-emissive iridium(III) complex, IrNPh2, featuring “aggregation-induced emission” (AIE) properties and used for sensitive oxygen sensing. IrNPh2 exhibits dual emissions at 450 and 515 nm, with 515 nm triplet-state emission demonstrating remarkable oxygen sensitivity due to its long-lived excited state (12.12 μs) and high quantum yield (68%). Stern–Volmer analysis reveals a notable quenching constant (Ksv = 12.44%–1) and an ultralow detection limit of 0.0397%, emphasizing its superior performance. The oxygen quenching mechanism is driven by electron transfer (ET), supported by computational studies showing the lowest-unoccupied molecular orbital (LUMO) alignment of IrNPh2 with the πg* orbitals of triplet oxygen, leading to superoxide radical (O2•–) formation. Electron paramagnetic resonance (EPR) studies further confirm this pathway. Biological evaluations using a three-dimensional (3D) U87-MG glioma spheroid model highlight the ability of IrNPh2 to detect hypoxic regions, with significant fluorescence enhancement under hypoxia and minimal cytotoxicity (>80% viability at 100 μM). With high sensitivity, low detection limits, and biocompatibility, IrNPh2 emerges as a promising candidate for oxygen sensing in environmental and biomedical applications, especially tumor hypoxia detection.Item In vitro hemolysis and lipid peroxidation-inducing activity of the tentacle extract of the sea anemone (Paracondylactis indicus Dave) in rat erythrocytes(Wolters Kluwer, 2007-06) Roy, AniruddhaIn vitro hemolytic activity of the tentacle extract of Paracondylactis indicus (Dave), a sea anemone found in the eastern coastal region of West Bengal (India), was determined in rat erythrocytes