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Two new transition metal complexes of a dipyrazinylpyridine (dppy) ligand 3,4-diethoxyphenyl-2,6-di(pyrazine-2-yl)pyridine L, {[CuL2]Cl2 (1) and [ZnL2]Cl2 (2)}, have been synthesized and characterized using NMR (for L and 2), UV-vis spectroscopy, ESR (for 1), HRMS, elemental analysis and DFT study. Upon interaction with bovine serum albumin (BSA), complexes 1 and 2 demonstrated varying binding capabilities, with 1 displaying superior binding (binding constant 4.5 x 104 M-1) towards BSA than 2 (binding constant 1.2 x 104 M-1). Similarly, with calf-thymus DNA (ct-DNA), 1 showed better binding affinity (1.1 x 106 M-1) than 2 (8.5 x 105 M-1) as observed from UV-visible spectroscopy. The mechanism that leads to the quenching of BSA fluorescence by 1 and 2 is attributed to static quenching. The complexes demonstrated an intercalative binding mode with ct-DNA, and molecular docking has been employed to elucidate the biomolecular interactions with the complexes. Circular dichroism spectra have been utilized to confirm the binding and assessment of the interactions with the biomolecules. Furthermore, studies of the anticancer potentials of 1-2 were evaluated using the Dalton's lymphoma (DL) cancer cell line. Following 48 hours of treatment, the IC50 values for 1 and 2 were identified as 24 mM and 28 mM, respectively, indicating their potency in inhibiting cancer cell growth. [ABSTRACT FROM AUTHOR]

Background: The pitcher plant, Nepenthes khasiana is utilized by several indigenous groups in Meghalaya, India owing to its medicinal properties. Due to their therapeutic qualities, a pioneer work was undertaken where the GC-MS technique was used to detect and identify the phytochemical substances present in the unopened pitcher fluids of N. khasiana. Materials and methods: Sample preparation and extraction of the methanol fraction of N. khasiana pitcher fluid were done following standard methods and exposed to GC-MS for phytochemical profiling. Results: The GC-MS study revealed 22 compounds in total, each of which had different phytochemical properties. The metabolites present were coronavirus inhibitors, antioxidants, antimicrobials, cure urolithiasis, hypocholesterolemic, and can cure cancer. Lipinski's Rule of 5 also depicted that 19 compounds of 22 have the potential to make active oral drugs for humans. Conclusion: The metabolites present in pitcher fluids could be used in drug formulation in pharmacology. Even, the fluids can be used as raw medicine for poor people owing to their medicinal properties as depicted in GC-MS however, further research on quantitative and qualitative investigation, its clinical trial on animals along with cytotoxic study are required for a concrete conclusion. [ABSTRACT FROM AUTHOR]

Tinospora cordifolia (TC), a medicinal plant deeply integrated into India's folklore and Ayurvedic medical tradition, has been a reliable remedy for addressing various health concerns. Despite its proven efficacy in managing diseases, it is essential to exercise prudence regarding its dosage, as excessive consumption may result in undesirable consequences. This present study seeks to ascertain if the methanolic extract of TC triggers any adverse effects on organ function, haematological parameters, or biochemical profiles. The extract was administered intra peritoneally (IP) into the Swiss albino mice at a concentration of 300mg/kg body weight and observations were taken on 7th and 14th day. In comparison to control groups, the levels of haemoglobin (Hb), packed cell volume (PVC), red blood corpuscles (RBC), red cell distribution width (RCW), and platelet count increase. However, significant decrease was also observed in the levels of erythrocyte sedimentation rate (ESR) and lymphocytes. Blood biochemical analysis reveals a significant increase in urea but a subsequent decrease in blood sugar levels. The findings unequivocally illustrate the disruption in the seminiferous tubules of the testis, accompanied by a decrease in spermatid count. Furthermore, observable damage to kidney tissues was noted. Based on these observations, it can be inferred that, despite its multifaceted therapeutic applications, TC extract may exert toxic effects in mice. [ABSTRACT FROM AUTHOR]

Curcuma longa Linn. (Turmeric) is a perennial herb known for its medicinal properties and is a common ingredient in Ayurvedic medicine, used for the prevention and treatment of several health disorders. Turmeric is also used as a common product in traditional pest management practices in India. As the pertinent problems associated with long-time exposure to chemical insecticides are becoming well known, the search for more eco-friendly alternatives has become necessary. In the present study, we aim to understand the efficiency of turmeric as a potent botanical against the common stored grain pest of legumes, Callosobruchus chinensis. Computer–based in-silico techniques are used as they allow a faster and more precise assessment of drug action. Direct toxicity tests are performed and the results are corroborated with the in-silico simulations to confirm the efficacy of turmeric as a potent botanical in management of C. chinensis. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the repurposing potential of existing antiviral drug candidates (FDA‐approved and investigational) against SARS‐CoV‐2 target proteins that facilitates viral entry and replication into the host body. To evaluate molecular affinities between antiviral drug candidates and SARS‐CoV‐2 associated target proteins such as spike protein (S) and main protease (Mpro), a molecular interaction simulation was performed by docking software (MVD) and subsequently the applicability score was calculated by machine learning algorithm. Furthermore, the STITCH algorithm was used to predict the pharmacology network involving multiple pathways of active drug candidate(s). Pharmacophore features of active drug(s) molecule was also determined to predict structure–activity relationship (SAR). The molecular interaction analysis showed that cordycepin has strong binding affinities with S protein (−180) and Mpro proteins (−205) which were relatively highest among other drug candidates used. Interestingly, compounds with low IC50 showed high binding energy. Furthermore, machine learning algorithm also revealed high applicability scores (0.42–0.47) of cordycepin. It is worth mentioning that the pharmacology network depicted the involvement of cordycepin in different pathways associated with bacterial and viral diseases including tuberculosis, hepatitis B, influenza A, viral myocarditis, and herpes simplex infection. The embedded pharmacophore features with cordycepin also suggested strong SAR. Cordycepin's anti‐SARS‐CoV‐2 activity indicated 65% (E‐gene) and 42% (N‐gene) viral replication inhibition after 48h of treatment. Since, cordycepin has both preclinical and clinical evidences on antiviral activity, in addition the present findings further validate and suggest repurposing potential of cordycepin against COVID‐19. [ABSTRACT FROM AUTHOR]

Southeast Asia, especially India, is well known for the highest use of smokeless tobacco. These products are known to induce oral squamous cell carcinoma. However, not all long-term tobacco-chewers develop oral squamous cell carcinoma. In addition, germline variants play a crucial role in susceptibility, prognosis, development, and progression of the disease. These prompted us to study the genetic susceptibility to oral squamous cell carcinoma among the long-term tobacco-chewers. Here, we presented a retrospective study on prolonged tobacco-chewers of Northeast India to identify the potential protective or risk-associated germline variants in tobacco-related oral squamous cell carcinoma along with HPV infection. Targeted re-sequencing (n = 60) of 170 genetic regions from 75 genes was carried out in Ion-PGM- and validation (n = 116) of the observed variants was done using Sequenom iPLEX MassARRAY- platform followed by polymerase chain reaction-based HPV genotyping and p16-immunohistochemistry study. Subsequently, estimation of population structure, different statistical and in silico approaches were undertaken. We identified one nonsensemediated mRNA decay transcript variant in the DFNA5 region (rs2237306), associated with Benzo(a)pyrene, as a protective factor (odds ratio = 0.33; p = 0.009) and four harmful (odds ratio.2.5; p\0.05) intronic variants, rs182361, rs290974, and rs169724 in SYK and rs1670661 in NELL1 region, involved in genetic susceptibility to tobacco- and HPVmediated oral oncogenesis. Among the oral squamous cell carcinoma patients, 12.6% (11/87) were HPV positive, out of which 45.5% (5/11) were HPV16-infected, 27.3% (3/11) were HPV18-infected, and 27.3% (3/11) had an infection of both subtypes. Multifactor dimensionality reduction analysis showed that the interactions among HPV and NELL1 variant rs1670661 with age and gender augmented the risk of both non-tobacco- and tobacco-related oral squamous cell carcinoma, respectively. These suggest that HPV infection may be one of the important risk factors for oral squamous cell carcinoma in this population. Finally, we newly report a DFNA5 variant probably conferring protection via nonsensemediated mRNA decay pathway against tobacco-related oral squamous cell carcinoma. Thus, the analytical approach used here can be useful in predicting the population-specific significant variants associated with oral squamous cell carcinoma in any heterogeneous population. [ABSTRACT FROM AUTHOR]

Development of environmentally benign catalyst systems, especially those derived from readily available nature's pool, in multicomponent synthesis, consolidates multiple facets of green chemistry. Here, an L-proline derived green acid catalyst in the form of L-proline⋅H 2 SO 4 was developed and employed for multicomponent synthesis of coumarin-based spiroindolino-3,4-dihydropyrimidin-2(1H)-ones from the reaction of 4-hydroxycoumarin, isatin and urea/thiourea. Preliminary cytotoxicity studies showed that a couple of compounds (M5 and M6) have good cytotoxicity (40-50%) against in Dalton's Lymphoma (DL) cells while demonstrating minimal cytotoxicity (10-12%) for normal non-cancerous cell lines. Molecular docking simulations for the least and most cytotoxic compounds, M3 and M6 respectively, against nineteen tumor target proteins were carried out, and seven of them were identified to test against all the sixteen compounds. Based on the estimated docking score and inhibition constants (K i ), the interaction of the compounds with the tumor target protein, beta-hexosaminidase B (PDB ID: 1NOW) matched closely with in vitro cytotoxicity data., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Spike protein and main proteases of SARS-CoV-2 have been identified as potential therapeutic targets and their inhibition may lead to the reticence of viral entry and replication in the host body. Despite several efforts; till now no specific drugs are available to treat SARS-CoV-2. Considering all these challenges, the main objective of the present study was to establish therapeutic potential of cordycepin against COVID-19 as a conventional therapeutic strategy. In the present study; molecular interaction study was performed to assess potential binding affinity of cordycepin with SARS-CoV-2 target proteins using computational approach. Additionally, network pharmacology was used to understand cordycepin-protein interactions and their associated pathways in human body. Cordycepin is under clinical trial (NCT00709215) and possesses structural similarity with adenosine except that, it lacks a 3' hydroxyl group in its ribose moiety and hence it served as a poly(A) polymerase inhibitor and terminate premature protein synthesis. Additionally, it is known that functional RNAs of SARS-CoV-2 genome are highly 3'-plyadenylated and leading to synthesis of all viral proteins and if cordycepin can destabilize SARS-CoV-2 RNAs by inhibiting polyadenylation process then it may step forward in terms of inhibition of viral replication and multiplication in the host. Moreover, cordycepin showed strong binding affinity with SARS-CoV-2 spike protein (-145.3) and main proteases (-180.5) that further corroborate therapeutic potential against COVID-19. Since cordycepin has both pre-clinical and clinical information about antiviral activities, therefore; it is suggested to the world community to undertake repurposing cordycepin to test efficacy and safety for the treatment of COVID-19.