Recent drug design strategies and identification of key heterocyclic scaffolds for promising anticancer targets.

Cancer, a noncommunicable disease, is the leading cause of mortality worldwide and is anticipated to rise by 75% in the next two decades, reaching approximately 25 million cases. Traditional cancer treatments, such as radiotherapy and surgery, have shown limited success in reducing cancer incidence. As a result, the focus of cancer chemotherapy has switched to the development of novel small molecule antitumor agents as an alternate strategy for combating and managing cancer rates. Heterocyclic compounds are such agents that bind to specific residues in target proteins, inhibiting their function and potentially providing cancer treatment. This review focuses on privileged heterocyclic pharmacophores with potent activity against carbonic anhydrases and kinases, which are important anticancer targets. Evaluation of ongoing pre-clinical and clinical research of heterocyclic compounds with potential therapeutic value against a variety of malignancies as well as the provision of a concise summary of the role of heterocyclic scaffolds in various chemotherapy protocols have also been discussed. The main objective of the article is to highlight key heterocyclic scaffolds involved in recent anticancer drug design that demands further attention from the drug development community to find more effective and safer targeted small-molecule anticancer agents.

Recent biological applications of heterocyclic hybrids containing s-triazine scaffold.

s-Triazine possesses an auspicious status in the field of drug discovery and development owing to its presence in many naturally occurring compounds as well as commercially available drugs like enasidenib, gedatolisib, bimiralisib, atrazine, indaziflam, and triaziflam. Easy, cost-effective, and efficient access to its derivatives in addition to their splendid biological activities such as anticancer, anti-inflammatory, antiviral, anticonvulsant, anti-tubercular, antidiabetic, antimicrobial, makes it an attractive heterocyclic nucleus in the field of medicinal chemistry. Other than the direct access of its derivatives from simple commercially available starting materials like amidine, the s-triazine derivatives have also been obtained starting from an inexpensive commercially available 2,4,6-trichloro-1,3,5-triazine (TCT) commonly known as cyanuric chloride. Owing to the high reactivity and the possibility of sequential substitution of TCT, a variety of biologically active heterocyclic scaffolds have been installed on this nucleus in order to have more potent compounds. These s-triazine-based heterocyclic hybrids have been reported to show enhanced biological activities in recent years. Therefore, it is important to summarize and highlight recent examples of these hybrids which is imperative to attract the attention of the drug development community.

Seroprevalence of SARS-CoV-2 infection among blue-collar workers in United Arab Emirates

Background: This is one of the first studies exploring immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among blue-collar workers in Abu Dhabi. Aims: This study estimated the seroprevalence of SARS-CoV-2 infection among workers living in a closed setting using qualitative analysis of the total SARS-CoV-2 antibody immune response. Methods: We conducted this monocentric, prospective, observational study in a labor compound for a cohort of workers between 28 March and 6 July 2020. We tested for SARS-CoV-2 (nasopharyngeal) (RT-PCR) and anti-SARS-CoV-2 T-Ab. Results: Out of a total of 1600 workers, 1206 (75.0%) participated in the study – all were males, median age 35 years (19–63 years). We found 51% of the participants to be positive for SARS-CoV-2; the 49.0% who tested negative were considered as contacts. Anti-SARS-CoV-2 T-Ab was detected among 864 participants, showing an overall point prevalence of 71.6%. A relatively higher response was found among cases (89.0%) than among contacts (53.2%). Conclusion: This study highlights the need to prioritize public health interventions in closed settings where disease transmission is higher due to greater overall exposure. A high seroprevalence of anti-SARS-CoV-2 T-Ab was found among the residents. A serial quantitative study applying time series and regression models is recommended to further evaluate the sustainability of the immune response among this and similar population groups.

Antimicrobial susceptibility of bacteraemic isolates of Salmonella enterica serovar typhi and paratyphi infection in Pakistan from 2017-2020.

OBJECTIVE: To determine the antibacterial susceptibility pattern of bacteraemia isolates of Salmonella enterica serovar typhi and paratyphi. METHODS: The retrospective descriptive observational study was conducted at the Microbiology section of Dow Diagnostic Research and Reference Laboratory, and comprised blood culture reports from January 1, 2017, to Dec 30, 2020, which were screened for the presence of Salmonella typhi and paratyphi growth The frequency of the isolates and their antibiotic resistance patterns were analysed. Data was analysed using SPSS 20. RESULTS: Of the 174,190 blood culture samples, 62,709(36%) were positive for bacterial growth. Salmonella were isolated in 8,689(13.8%) samples of which 8,041(92.5%) were Salmonella typhi, 529(6%) were Salmonella paratyphi A and 119(1.3%) were Salmonella paratyphi B. There was a drastic increase in resistance to third-generation cephalosporin in Salmonella typhi from 71(12.8%) in 2017 to 1,420(71%) in 2018, 2,850(74.6%) in 2019 and 1,251(77%) in 2020. All isolates were sensitive to meropenem and azithromycin. CONCLUSIONS: A high number of extensively drug-resistant typhoid cases due to Salmonella typhi were found. All isolates were sensitive to meropenem and azithromycin.

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches.

Type II diabetes mellitus (T2DM) is a global health issue with high rate of prevalence. The inhibition of α-glucosidase enzyme has prime importance in the management of T2DM. This study was established to synthesize Schiff bases of 1,3-dipheny urea (3a-y) and to investigate their in vitro anti-diabetic capability via inhibiting α-glucosidase, a key player in the catabolism of carbohydrates. The structures of all compounds were confirmed through various techniques including, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) and mass-spectrometry (MS) methods. Interestingly all these compounds displayed potent inhibition IC50 values in range of 2.14-115 µM as compared to acarbose used as control. Additionally, all the compounds were docked at the active site of α-glucosidase to predict their mode of binding. The docking results indicates that Glu277 and Asn350 play important role in the stabilization of these compounds in the active site of enzyme. These molecules showed excellent predicted pharmacokinetics, physicochemical and drug-likeness profile. The anti-diabetic potential of these molecules signifies their medical importance and provide insights into prospective therapeutic options for the treatment of T2DM.

Synthetic α-glucosidase inhibitors as promising anti-diabetic agents: Recent developments and future challenges.

Diabetes mellitus is one of the biggest challenges for the scientific community in the 21st century. It is a well-recognized multifactorial health problem contributes significantly to high mortality rates by causing serious health complications mainly related to cardiovascular diseases, kidney damage and neuropathy. The inhibition of α-glucosidase (enzyme that catalyses starch hydrolysis in the intestine) is an effective therapeutic approach for controlling hyperglycemia associated with type-2 diabetes. However, the presently approved drugs/inhibitors such as acarbose, miglitol and voglibose have several undesirable gastrointestinal side effects impeding their applications. Therefore, search for novel and more effective inhibitors with reduced side effects and less cost remains a fascinating area of research. In this context, a large variety of α-glucosidase inhibitors have been identified in recent years that demands attention from drug development community. This review is therefore an effort to summarize and highlight the promising α-glucosidase inhibitors especially those which are primarily based on aromatic heterocyclic scaffolds such as coumarin, imidazole, isatin, pyrimidine, quinazoline, triazine, thiazole etc, having improved safety and pharmacological profiles.

Molecular duplexes featuring NH···N, CH···O and CH···π interactions in solid-state self-assembly of triazine-based compounds.

Synthetic supramolecular structures constructed through the cooperative action of numerous non-covalent forces are highly desirable as models to unravel and understand the complexity of systems created in nature via self-assembly. Taking advantage of the low cost of 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride) and the sequential nucleophilic substitution reactions with almost all types of nucleophiles, a series of six structurally related novel s-triazine derivatives 1-6 were synthesized and structurally characterized based on their physical, spectral and crystallographic data. The solid-state structures of all the six compounds showed intriguing and unique molecular duplexes featuring NH···N, CH···O and CH···π interactions. Careful analysis of different geometric parameters of the involved H-bonds indicates that they are linear, significant and are therefore responsible for guiding the three-dimensional structure of these compounds in the solid state. The prevalence of sextuple hydrogen bond array-driven molecular duplexes and the possibility of structural modifications on the s-triazine ring render these novel triazine derivatives 1-6 attractive as a platform to create heteroduplex constructs and their subsequent utility in the field of supramolecular chemistry and crystal engineering.

Phenoxy pendant isatins as potent α-glucosidase inhibitors: reciprocal carbonyl⋯carbonyl interactions, antiparallel π⋯π stacking driven solid state self-assembly and biological evaluation.

Carbonyl-carbonyl (CO⋯CO) interactions are recently explored noncovalent interactions of significant interest owing to their role in the stability of biomacromolecules. Currently, substantial efforts are being made to understand the nature of these interactions. In this study, twelve phenoxy pendant isatins 1-12 have been evaluated for their α-glucosidase inhibitory potential in addition to the analysis of X-ray single crystals of 4 and 9. Both compounds 4 and 9 showed intriguing and unique self-assembled structures. The CO⋯CO and antiparallel displaced π⋯π stacking interactions are mainly involved in the formation of 1D-stair like supramolecular chains of 4 whereas antiparallel π⋯π stacking interactions drive the formation of 1D-columnar stacks of 9. These compounds not only highlight the potential of the isatin moiety in forming strong CO⋯CO and antiparallel π⋯π stacking interactions but also are interesting models to provide considerable insight into the nature of these interactions. The in vitro biological studies revealed that all twelve phenoxy pendant isatins 1-12 are highly potent inhibitors of α-glucosidase enzyme with IC50 values ranging from 5.32 ± 0.17 to 150.13 ± 0.62 µM, showing many fold more potent activity than the standard drug, acarbose (IC50 = 873.34 ± 1.67). Easy access and high α-glucosidase inhibition potential of these phenoxy pendant isatins 1-12 provide an attractive platform for finding more effective medication for controlling postprandial hyperglycemia.

Synthesis, solid state self-assembly driven by antiparallel π⋯π stacking and {⋯H-C-C-F}2 dimer synthons, and in vitro acetyl cholinesterase inhibition activity of phenoxy pendant isatins.

A series of novel phenoxy pendant isatins PI1-12 have been synthesized in excellent yields by a simple nucleophilic substitution reaction involving isatins and 1-(2-bromoethoxy)-4-substituted benzenes, and characterized by their FT-IR, 1H NMR, 13C NMR and GC-MS data, and in the case of PI4 by its single crystal X-ray analysis. The solid-state structure of PI4 showed an intriguing and unique 1D-supramolecular chain-based self-assembled structure, the driving force of which is mainly the strong antiparallel π⋯π stacking and {⋯H-C-C-F}2 dimer synthons. This compound not only highlights the potential of the isatin moiety in forming strong antiparallel π⋯π stacking interactions but also provides a platform to have considerable insight into the nature, strength and directionality of much debated π-π and C-H⋯F-C interactions. The in vitro biological studies revealed that three phenoxy pendant isatins PI1, PI2 and PI4 are highly potent inhibitors of acetylcholinesterase enzyme with IC50 values of 0.52 ± 0.073 µg ml-1, 0.72 ± 0.012 µg ml-1 and 0.68 ± 0.011 µg ml-1, respectively, showing comparable activity to the standard drug, donepezil (IC50 = 0.73 ± 0.015 µg ml-1). A simple and efficient synthesis of phenoxy pendant isatins PI1-12 from inexpensive and commercially available starting materials, and their high potential of acetyl cholinesterase inhibition provide an attractive opportunity to find more effective medication for Alzheimer's disease (AD).

Utilization of transition metal fluoride-based solid support catalysts for the synthesis of sulfonamides: carbonic anhydrase inhibitory activity and in silico study.

The applications of solid support catalysts in catalyzing organic reactions are well-evident. In the present study, we explored a transition metal fluoride (FeF3) adsorbed on molecular sieves (4 Å) as a solid support catalyst for the preparation of sulfonamides 3a-3o. The solid support catalyst was characterized via X-ray diffraction and AFM analysis. The catalyst was further explored for the synthesis of indoles 6a-h, 1H-tetrazoles and 1,4-dihydropyridines. The sulfonamides prepared herein were investigated for their potential to inhibit carbonic anhydrase (hCA II, hCA IX and hCA XII). All compounds were found to be active inhibitors with IC50 values in the low micromolar range. Some compounds were even found to be highly selective inhibitors. Compound 3i only inhibited hCA II (IC50 = 2.76 ± 1.1 µM) and had <27% inhibition against hCA IX and hCA XII. Similarly, 3e (IC50 = 0.63 ± 0.14 µM) only inhibited hCA XII and showed <31% inhibition against hCA II and hCA IX. Molecular docking studies were carried out to rationalize the ligand-binding site interactions. Given the lack of selective CA inhibitors, compounds 3e and 3i can provide significant leads for the further development of highly selective CA inhibitors.

Synthesis, structure and acetylcholinesterase inhibition activity of new diarylpyrazoles.

A variety of diarylpyrazole derivatives III-VI were synthesized and structurally characterized using FTIR, 1H and 13C NMR spectroscopy, and in case of compound VIb by X-ray single crystal analysis. The in vitro biological studies revealed that seven of the diarylpyrazole derivatives IIIa, IIIb, IIId, IIIe, IVa, IVb and IVd are highly potent inhibitors of acetylcholinesterase enzyme with IC50 values of 0.48 ± 0.092 µg/mL, 0.45 ± 0.093 µg/mL, 0.30 ± 0.014 µg/mL, 0.59 ± 0.072 µg/mL, 0.29 ± 0.084 µg/mL, 0.56 ± 0.010 µg/mL and 0.28 ± 0.096 µg/mL, respectively. All these seven products were more potent than the standard drug, donepezil (IC50 = 0.73 ± 0.015 µg/mL), while compounds IIIc (0.67 ± 0.099 µg/ml) and VIa (0.66 ± 0.069 µg/ml) are almost equipotent to the donepezil. Particularly, compounds IVa and IVd are highly active acetylcholinesterase enzyme inhibitors, demonstrating more than two-fold inhibitory activity than the reference inhibitor. Molecular docking studies were carried out to identify the possible binding modes of the diarylpyrazoles within the active pocket of the enzymes. The docking interactions of the synthesized compounds with acetylcholinesterase also provided high docking scores. These results clearly indicate the potential of these compound as powerful lead molecules for further investigations.

Isatin-hydrazide conjugates as potent α-amylase and α-glucosidase inhibitors: Synthesis, structure and invitro evaluations.

Managing diabetes that is a global life-threatening problem, remains a challenge for the scientific community. The inhibition of α-amylase and α-glucosidase enzymes which are responsible for the digestion of dietary carbohydrates is an effective strategy to control postprandial hyperglycemia. Herein, we report the novel and highly potent inhibitors of α-amylase and α-glucosidase, namely isatin-hydrazide conjugates 1a - 1j that are easily accessed in two steps from simple and inexpensive commercially available isatin. The in vitro bio-evaluations of these compounds revealed that conjugates 1a, 1h and 1f are highly potent inhibitors of α-amylase with IC50 values of 19.6, 12.1 and 18.3 µg/ml, respectively as compared to the standard, acarbose (IC50 = 36.2 µg/ml). Similarly, the conjugates 1a, 1b, 1d, 1f and 1i showed significant activity against α-glucosidase with IC50 values of 14.8, 25.6, 13.2, 14.5 and 16.5 µg/ml, respectively as compared to the acarbose (IC50 = 34.5 µg/ml). Notably, the compounds 1a and 1f were found to be highly potent against both α-amylase and α-glucosidase enzymes, demonstrating about two-fold better inhibitory activity than the reference inhibitor. Molecular docking studies were performed to recognize the possible binding modes of the compounds with the active pocket of the enzymes. The results of this study divulge the potential of these compounds as powerful and inexpensive lead molecules for future investigations.

Group B streptococcus sepsis in an infant presented with cellulitis of soft tissue of neck.

We report a case of cellulitis of the soft tissue of the neck with group B streptococcus (GBS) sepsis in a 4-week-old baby boy presented with a 1-day history of fever, irritability and feed refusal. While in the hospital, a left-sided submandibular swelling extending to preauricular area started emerging, which progressed dramatically. Ultrasound scan of the neck confirmed inflammation of the underlying soft tissue while revealing multiple enlarged lymph nodes without any abscess formation and overlying soft tissue oedema. Blood cultures were flagged positive at 9 hours for GBS. The infant was treated with intravenous antibiotics for 2 weeks. GBS is considered a common cause of early-onset sepsis in neonates. However, it can also lead to late-onset sepsis in infancy with variable presentations. In our case, GBS sepsis manifested with cellulitis of the soft tissue of the neck along with swelling of local lymph nodes.

Multi-step rainfall forecasting using deep learning approach.

Rainfall prediction is immensely crucial in daily life routine as well as for water resource management, stochastic hydrology, rain run-off modeling and flood risk mitigation. Quantitative prediction of rainfall time series is extremely challenging as compared to other meteorological parameters due to its variability in local features that involves temporal and spatial scales. Consequently, this requires a highly complex system having an advance model to accurately capture the highly non linear processes occurring in the climate. The focus of this work is direct prediction of multistep forecasting, where a separate time series model for each forecasting horizon is considered and forecasts are computed using observed data samples. Forecasting in this method is performed by proposing a deep learning approach, i.e, Temporal Deep Belief Network (DBN). The best model is selected from several baseline models on the basis of performance analysis metrics. The results suggest that the temporal DBN model outperforms the conventional Convolutional Neural Network (CNN) specifically on rainfall time series forecasting. According to our experimentation, a modified DBN with hidden layes (300-200-100-10) performs best with 4.59E-05, 0.0068 and 0.94 values of MSE, RMSE and R value respectively on testing samples. However, we found that training DBN is more exhaustive and computationally intensive than other deep learning architectures. Findings of this research can be further utilized as basis for the advance forecasting of other weather parameters with same climate conditions.

Novel coumarin-isatin hybrids as potent antileishmanial agents: Synthesis, in silico and in vitro evaluations.

Leishmaniasis being one of the six major tropical diseases that affects nearly 0.7-1.3 million people annually, has so far limited and high toxic therapeutic options. Herein, we report the synthesis, in silico, and in vitro evaluations of novel coumarin-incorporated isatin hydrazones (Spf-1 - Spf-10) as highly potent and safe antileishmanial agents. Molecular docking was initially carried out to decipher the binding confirmation of lead molecules towards the active cavity of the target protein (Leishmanolysin gp63) of Leishmania tropica. Among all the docked compounds, only Spf-6, Spf-8, and Spf-10 showed high binding affinities due to a pattern of strong conventional hydrogen bonds and hydrophobic π-interactions. The molecular dynamics simulations showed the stable pattern of such bonding and structure-based confirmation with a time scale of 50 ns towards the top compound (Spf-10) and protein. These analyses affirmed the high stability of the system. Three out of ten compounds evaluated for their antileishmanial activity against Leishmania tropica promastigotes and amastigotes were found to be active at micromolar concentrations (IC50 range 0.1-4.13 µmol/L), and most importantly, they were also found to be highly biocompatible when screened for their toxicity in human erythrocytes.

Exploration of Chromone-Based Thiosemicarbazone Derivatives: SC-XRD/DFT, Spectral (IR, UV-Vis) Characterization, and Quantum Chemical Analysis.

By the condensation of thiosemicarbazide with coumarin aldehyde, two novel substituted thiosemicarbazones with chemical formulae C24H25N3O3S (3a) and C26H23N3O3S (3b) have been synthesized. The synthesized compounds were resolved using SC-XRD, and structure elucidation was carried out using 1H NMR, 13C NMR, UV-visible, and FT-IR spectroscopic analyses. Computational calculations at the B3LYP/6-311+G(d,p) level of theory were performed to countercheck the experimental (UV-vis, FT-IR) findings and explore the electronic (FMO, NBO, MEP) properties of 3a-b. The nonlinear optical (NLO) properties of 3a-b were estimated using B3LYP, HF, LC-BLYP, CAM-B3LYP, M062X, and M06 functionals in combination with the 6-311+G(d,p) basis set. The crystallographic data revealed that compounds were crystallized as an orthorhombic crystal lattice with the Pbcn space group and the triclinic crystal lattice with the P̅1 space group. A good concurrence among experimental SC-XRD-generated bond lengths, bond angles, FT-IR, UV-vis, and corresponding DFT results was found, which confirms the purity of both compounds. The NBO analysis confirmed the presence of intramolecular hydrogen bonding and hyperconjugative interactions, which not only were the pivotal cause of stability of the investigated compounds but also led to an overwhelming NLO response. The energy differences calculated for HOMO/LUMO are 3.053 and 3.118 eV in 3a and 3b, respectively. The crystal 3b showed a higher value of first-order polarizability at all levels of theory than 3a. Overall results show that the crystals under investigation are polarized in nature with a good dipole moment. A comparative analysis with urea molecules clearly indicates that the studied compounds are acceptable NLO candidates and they can be used for future technological applications.

Fluorescent organic nanoparticles (FONs) as convenient probes for metal ion detection in aqueous medium.

Recently, water contamination caused by metal ions has become one of the most serious problems as it has caused several deaths and socioeconomic problems around the world. Hence, the fast and accurate detection of metal ions in aqueous media has become the most important area of research; from time to time, new probes have been designed for this purpose. Among the previously reported sensors, probes based on fluorescent organic nanoparticles (FONs) have been gaining tremendous attention due to their ease of preparation/fabrication, synthetic diversity according to targeted metal ions, quick response, high selectivity toward different analytes at lower concentrations, tenable optical properties, and less toxicity. This review comprises two main sections, wherein we have tried to summarize the key progresses made in this field. The first section summarizes the literature dealing with FON-based chemosensors, which are used for the detection of transition metal ions of silver, copper, chromium, cadmium, mercury, iron, and zinc. The second section focuses on FON-based chemosensors that have been used for the detection of main group metal ions, namely, cesium, aluminum, strontium, lithium, and tin. Further, this review provides an adequate amount of information about the mechanism of metal ion sensing with FONs. It is expected that this review can provide sufficient information about this area of research and will be useful in fruitful progress in this field in the future.

A facile and concise route to (hydroxybenzoyl)pyrido[2,3-d]pyrimidine heterocycle derivatives: synthesis, and structural, spectral and computational exploration.

In this work, we report the efficient synthesis of novel (hydroxybenzoyl)pyrido[2,3-d]pyrimidine heterocycle derivatives: 6-(2-hydroxy-5-methylbenzoyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (6a), 6-(5-fluoro-2-hydroxybenzoyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (6b), 6-(5-ethyl-2-hydroxybenzoyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (6c) and 6-(2-hydroxy-5-isopropylbenzoyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (6d). The chemical structures of the title compounds were ascertained by spectral techniques including 1H, 13C NMR, UV-visible and FT-IR spectroscopy as well as single-crystal X-ray diffraction analysis. Additionally, density functional theory (DFT) and time-dependent (TD-DFT) computation were adopted to analyze the electronic structures of 6a-d. Compounds 6a-d were computed in the ground state for FT-IR spectroscopic and natural bond orbital (NBO) analysis by DFT/B3LYP with the 6-311+G(d,p) basis set. UV-vis spectroscopic and HOMO and LUMO energy values for 6a-d were determined via TD-DFT/B3LYP with the 6-311+G(d,p) basis set. The optimized geometric parameters, UV-vis findings, and vibrational frequencies indicate good consistency with the experimental data. NBO analysis was conducted to explore the interactions and charge transfer among different orbitals in the title compounds. The HOMO and LUMO band gap (ΔE) values for 6a-d were found to be 3.93, 3.91, 4.10 and 3.91 eV, respectively. Molecular electrostatic potential (MEP) analysis explored the reactivity of the title compounds by predicting their nucleophilic as well as electrophilic sites.

Xanthenone-based hydrazones as potent α-glucosidase inhibitors: Synthesis, solid state self-assembly and in silico studies.

Xanthenone based hydrazone derivatives (5a-n) have been synthesized as potential α-glucosidase inhibitors. All synthesized compounds (5a-n) are characterized by their FTIR, 1H NMR, 13C NMR and HRMS, and in case of 5g also by X-ray crystallographic technique. The compounds unveiled a varying degree of α-glucosidase inhibitory activity when compared with standard acarbose (IC50 = 375.38 ±â€¯0.12 µM). Amongst the series, compound 5l (IC50 = 62.25 ±â€¯0.11 µM) bearing a trifluoromethyl phenyl group is found to be the most active compound. Molecular modelling is performed to establish the binding pattern of the more active compound 5l, which revealed the significance of substitution pattern. The pharmacological properties of molecules are also calculated by MedChem Designer which determines the ADME (absorption, distribution, metabolism, excretion) properties of molecules. The solid state self-assembly of compound 5g is discussed to show the conformation and role of iminoamide moiety in the molecular packing.

Mesoporous bioactive glass-polyurethane nanocomposites as reservoirs for sustained drug delivery.

The materials capable of sustained drug release are highly desired in the biomedical field, and for this purpose, mesoporous bioactive glass (MBG) and polyurethanes (PUs) are being used along with various other materials. However, MBG is highly brittle and PUs suffer from the lower tensile strength value. Therefore, to overcome these shortcomings, bioactive nanocomposites were designed and fabricated by using MBG and biodegradable PUs. MBG with variable percentages was used as filler in arginine and starch-based PU matrices. The structural, mechanical and physicochemical properties were evaluated by fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), stress-strain curves and MTT assay. All the nanocomposites exhibited high cell viability (96-100%) and are therefore designated as biocompatible. The young's modulus is in the range of 0.5-0.8 MPa, which perfectly matches with that of cancellous bones. The nanocomposites were further studied for sustained drug delivery of an anti-cancer drug, imatinib. There was no burst effect and 52-84% of the drug was released over a period of three weeks. Consequently, these nanocomposites behaved as reservoirs for sustained drug release and can be applied for reducing the dose frequency where required.