Synthesis, crystal structure analysis, computational modelling and evaluation of anti-cervical cancer activity of novel 1,5-dicyclooctyl thiocarbohydrazone.

Thiocarbazones are widely used as bioactive and pharmaceutical intermediates in medicinal chemistry and have been shown to exhibit diverse biological and pharmacological activities such as antimicrobial, anticancer, anti-viral, anti-convulsant and anti-inflammatory etc. In continuation of our interest in biologically active heterocycles and in an attempt to synthesize a spiro derivative, 1,2,4,5-tetraazaspiro[5.7]tridecane-3-thione, herein, the synthesis of 1,5-dicyclooctyl thiocarbohydrazone (3) has been reported via reaction of the cyclooctanone and thiocarbohydrazide. The structure was assigned on the basis of detailed spectral analysis and also confirmed by X-ray crystal studies. The Hirshfeld surface analysis indicates that the most significant interaction is S⋯H (12.7%). The presentation of mechanistic aspects regarding the plausible route of its formation has also been included. The first hyperpolarizability (ß0) was found to be 10.22 × 10-30 esu, which indicates that the compound exhibits good non-linear optical properties. The density functional theory (DFT) method has been used to characterize the spectroscopic properties and vibrational analysis of 1,5-dicyclooctyl thiocarbohydrazone (3) theoretically. The compound and cisplatin (standard) were screened for their antiproliferative activity against the human cervical cancer cell line (SiHa) and they exhibited significant activity with IC50 values of 250 µM and 15 µM, respectively. The inhibitory nature of the title compound against viral oncoprotein E6 was confirmed by studies using molecular docking analysis. The results of biological activity and in silico analysis indicate that the synthesized molecule could act as a precursor for the synthesis of new heterocyclic derivatives of medicinal importance.

Studies on Methylpyrazole-Substituted Benzimidazoles to Target Helicobacter pylori Infection through HpIMPDH Inhibition.

The prevalence of Helicobacter pylori infection has been increasing rapidly due to the genetic heterogeneity and antibacterial resistance shown by the bacteria, affecting over 50% of the world population and over 80% of the Indian population, in particular. In this regard, novel drug targets are currently being explored, one of which is the crucial metabolic enzyme inosine-5'-monophosphate dehydrogenase (IMPDH) involved in the de novo nucleotide biosynthesis pathway, in order to combat the infection and devise efficient therapeutic strategies. The present study reports the development of methylpyrazole-substituted benzimidazoles as small molecule inhibitors of H. pylori IMPDH with a nanomolar range of enzyme inhibition. A set of 19 small molecules have been designed, synthesized, and further evaluated for their inhibitory potential against H. pylori IMPDH using in silico, in vitro, biochemical, and biophysical techniques. Compound 7j was found to inhibit H. pylori IMPDH with an IC50 value of 0.095 ± 0.023 µM, which is close to 1.5-fold increase in the inhibitory activity, in comparison to the previously reported benzimidazole-based hit C91. Moreover, kinetic characterization has provided significant insights into the uncompetitive inhibition shown by these small molecules on H. pylori IMPDH, thus providing details about the enzyme inhibition mechanism. In conclusion, methylpyrazole-based small molecules indicate a promising path to develop cheap and bioavailable drugs to efficiently treat H. pylori infection in the coming years, in comparison to the currently available therapy.

Effect of Differential Surface Anisotropy on Dissolution Behavior of Fenofibrate Crystal Habits: Comparative Study using USP Type 2 and Type 4 Dissolution Apparatuses.

The solid-state properties of active pharmaceutical ingredient (API) have significant impact on its dissolution performance. In the present study, two different crystal habits viz. rod and plate shape of form I of FEN were evaluated for dissolution profile using USP Type 2 and Type 4 apparatuses. Molecular basis of differential dissolution performance of different crystal habits was investigated. Rod (FEN-R) and plate (FEN-P) shaped crystal habits of Form I of FEN were generated using anti-solvent crystallization method. Despite the same polymorphic form and similar particle size distribution, FEN-P demonstrated higher dissolution performance than FEN-R. Crystal face indexation and electrostatic potential (ESP) map provided information on differential relative abundance of various facets and their molecular environment. In FEN-R, the dominant facet (001) is hydrophobic due to the exposure of chlorophenyl moiety. Whereas, in FEN-P the dominant facet (01-1) was hydrophilic due to the presence of chlorine and ester carbonyl groups. Deeper insight on the impact of different facets on dissolution behavior was obtained by energy framework analysis by unveiling strength of intermolecular interactions along various crystallographic facets. Moreover, type 4 apparatus provided higher discriminatory ability over USP Type 2 apparatus, in probing the crystal habit induced differential dissolution performance of FEN. The findings of this study emphasize that crystal habit should be considered as an important critical material attribute (CMA) during formulation development of FEN and due considerations should be given to the selection of the appropriate dissolution testing set-up for establishing in vitro-in vivo correlation.

To Explore the Binding Affinity of Human γ-Secretase Activating Protein (GSAP) Isoform 4 with APP-C99 Peptides.

γ-Secretase activating protein (GSAP) is known to play an important role in the ß-amyloid pathway. It acts as a modulator and accentuates the truncation of the amyloid precursor protein C-99 fragment through the γ-secretase complex. GSAP has four isoforms, out of which canonical isoform 1, a 16 kDa C-terminal portion, has been extensively studied, whereas the function of other three isoforms remains unknown. Here, we explore the GSAP isoform 4 (GSAP_I4) expression and purification from inclusion bodies followed by the refolding of the protein. The secondary structure of GSAP_I4 is predicted using circular dichroism. The protein is further characterized by western blotting and mass spectroscopy analysis. Additionally, biochemical assays and in silico molecular docking and molecular simulation are performed to investigate the binding of GSAP_I4 and APP-C99 peptide fragments. The results reflect that although GSAP_I1 and GSAP_I4 share high sequence similarity, the isoform 4 does not show any affinity toward APP-C99 peptide fragments. This hints toward the fact that GSAP_I4 might have a different role in the living system that is yet unexplored.

Synthesis, kinetics and cellular studies of new phenothiazine analogs as potent human-TLK inhibitors.

The alterations in the expression patterns of protein kinases often implicate human cancer initiation and progression. Human tousled-like kinases (TLKs), both TLK1/1B and TLK2, are evolutionary kinases found in cell signaling pathways and are involved in DNA repair, replication, and chromosomal integrity. Several reports have demonstrated the numerous roles of TLK1B in the development and progression of cancer via its interactions with different partners, and this direct association has made them viable molecular targets for cancer therapy. Previous studies have shown phenothiazines to be potent TLK1B inhibitors. Herein, we report the design and synthesis of a class of phenothiazine molecules and their biological inhibitory effect on hTLK1B/KD through in vitro kinase assays, cellular assays, and in silico studies. We identified a few inhibitors with better inhibition and physio-chemical properties than the reported TLK1B inhibitors using a recombinant human tousled-like kinase 1B-kinase domain (hTLK1B-KD). Very interestingly, inhibitory activity with LNCap cells was found to be on the sub-nanomolar level. Our attempts to study the newly designed phenothiazine analogs, as well as generate a stable catalytically active hTLK1B-KD in high yield, represent a fundamental step towards the structure-based design of future TLK-specific inhibitors.

New Signatures of Bio-Molecular Complexity in the Hypervelocity Impact Ejecta of Icy Moon Analogues.

Impact delivery of prebiotic compounds to the early Earth from an impacting comet is considered to be one of the possible ways by which prebiotic molecules arrived on the Earth. Given the ubiquity of impact features observed on all planetary bodies, bolide impacts may be a common source of organics on other planetary bodies both in our own and other solar systems. Biomolecules such as amino acids have been detected on comets and are known to be synthesized due to impact-induced shock processing. Here we report the results of a set of hypervelocity impact experiments where we shocked icy mixtures of amino acids mimicking the icy surface of planetary bodies with high-speed projectiles using a two-stage light gas gun and analyzed the ejecta material after impact. Electron microscopic observations of the ejecta have shown the presence of macroscale structures with long polypeptide chains revealed from LCMS analysis. These results suggest a pathway in which impact on cometary ices containing building blocks of life can lead to the synthesis of material architectures that could have played a role in the emergence of life on the Earth and which may be applied to other planetary bodies as well.

Mutants of Helicobacter pylori IMPDH: Kinetics and in silico Studies to Determine the Structural and Functional Role of Key Amino Acids.

The emergence of antibiotic-resistant strains of Helicobacter pylori necessitates the development of novel therapeutic strategies to fight against its infection. Recently, the enzyme inosine-5'-monophosphate dehydrogenase (IMPDH) has emerged as a promising target to treat bacterial infections due to its crucial role in the de novo purine biosynthesis pathway. The differences between the prokaryotic and eukaryotic IMPDHs, in the NAD+ binding domain and flap region, allow the identification of pathogen-specific inhibitors. In the present study, seven point mutants of wild type Helicobacter pylori IMPDH are constructed by site-directed mutagenesis, and characterized using in silico and kinetic studies. Point mutations in the NAD+ binding domain and the flap region are shown to impart significant changes in the enzyme's structure and function. In addition, the product inhibition characteristics of the Arg396-Tyr397 dyad (RY dyad) show that both the residues are important for water activation in the reaction. The results obtained are beneficial for the design and development of small-molecule inhibitors, capable of species-specific inhibition.

Swertiamarin mitigates nephropathy in high-fat diet/streptozotocin-induced diabetic rats by inhibiting the formation of advanced glycation end products.

CONTEXT: The molecular mechanism by which Swertiamarin (SM) prevents advanced glycation end products (AGEs) induced diabetic nephropathy (DN) has never been explored. OBJECTIVE: To evaluate the effect of SM in preventing the progression of DN in high fat diet-streptozotocin-induced diabetic rats. MATERIALS AND METHODS: After 1 week of acclimatisation, the rats were divided randomly into five groups as follows: (1) Control group, which received normal chow diet; (2) High-fat diet (HFD) group which was fed diet comprising of 58.7% fat, 27.5% carbohydrate and 14.4% protein); (3) Aminoguanidine (AG) group which received HFD + 100 mg/k.b.w.AG (intraperitoneal); (4) Metformin (Met) group which received HFD + 70 mg/k.b.w. the oral dose of Met and (5) SM group which was supplemented orally with 50 mg/k.b.w.SM along with HFD. After 12 weeks all HFD fed animals were given a single 35 mg/k.b.w. dose of streptozotocin with continuous HFD feeding for additional 18 weeks. Later, various biochemical assays, urine analyses, histopathological analysis of kidneys, levels of AGEs, expression of various makers, and in-silico analysis were performed. RESULTS: The diabetic group demonstrated oxidative stress, increased levels of AGEs, decreased renal function, fibrosis in the renal tissue, higher expression of the receptor for advanced glycation end products (RAGE), which were ameliorated in the SM treated group. In-silico analysis suggests that SM can prevent the binding of AGEs with RAGE. CONCLUSIONS: SM ameliorated DN by inhibiting the oxidative stress induced by AGEs.HighlightsSM reduces the levels of hyperglycaemia-induced advanced glycation end products in serum and renal tissue.SM prevents renal fibrosis by inhibiting the EMT in the kidney tissue.The in-silico analysis proves that SM can inhibit the binding of various AGEs with RAGE, thereby inhibiting the AGE-RAGE axis.

Structural Insights of Three 2,4-Disubstituted Dihydropyrimidine-5-carbonitriles as Potential Dihydrofolate Reductase Inhibitors.

In this report, we describe the structural characterization of three 2,4-disubstituted-dihydropyrimidine-5-carbonitrile derivatives, namely 2-{[(4-nitrophenyl)methyl]sulfanyl}-6-oxo-4-propyl-1,6-dihydropyrimidine-5-carbonitrile 1, 4-(2-methylpropyl)-2-{[(4-nitrophenyl)methyl]sulfanyl}-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 2, and 2-[(2-ethoxyethyl)sulfanyl]-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile monohydrate 3. An X-ray diffraction analysis revealed that these compounds were crystallized in the centrosymmetric space groups and adopt an L-shaped conformation. One of the compounds (3) crystallized with a water molecule. A cyclic motif (R22(8)) mediated by N-H···O hydrogen bond was formed in compounds 1 and 2, whereas the corresponding motif was not favorable, due to the water molecule, in compound 3. The crystal packing of these compounds was analyzed based on energy frameworks performed at the B3LYP/6-31G(d,p) level of theory. Various inter-contacts were characterized using the Hirshfeld surface and its associated 2D-fingerprint plots. Furthermore, a molecular docking simulation was carried out to assess the inhibitory potential of the title compounds against the human dihydrofolate reductase (DHFR) enzyme.

Shock Processing of Amino Acids Leading to Complex Structures-Implications to the Origin of Life.

The building blocks of life, amino acids, are believed to have been synthesized in the extreme conditions that prevail in space, starting from simple molecules containing hydrogen, carbon, oxygen and nitrogen. However, the fate and role of amino acids when they are subjected to similar processes largely remain unexplored. Here we report, for the first time, that shock processed amino acids tend to form complex agglomerate structures. Such structures are formed on timescales of about 2 ms due to impact induced shock heating and subsequent cooling. This discovery suggests that the building blocks of life could have self-assembled not just on Earth but on other planetary bodies as a result of impact events. Our study also provides further experimental evidence for the 'threads' observed in meteorites being due to assemblages of (bio)molecules arising from impact-induced shocks.

Recombinant Tumor Suppressor TSC1 Differentially Interacts with Escherichia coli DnaK and Human HSP70.

Tuberous sclerosis complex (TSC) is a neurological syndrome manifested by non-cancerous tumors in several organs. Mutations in either TSC1 or TSC2 tumor suppressor gene cause the disease. In the cell, TSC1 is known to form a heterodimer with TSC2 because of which an active complex is formed that negatively regulates the mTORC1 activity during cellular stress. Hence, mutation in TSC1 or TSC2 is manifested by excess proliferation of the cells leading to the development of numerous benign tumors. The TSC1 and TSC2 complex is known to interact with several protein-binding partners. One such significant interaction of this complex is with the molecular chaperone HSP70. The role of TSC1 in that interaction is still elusive. Here, we have expressed and purified TSC1 (302-420 residues) in a bacterial expression system and have shown that this region directly interacts with HSP70. We have shown that TSC1 increases the ATPase activity of Escherichia coli DnaK, a HSP70 homologue. On the contrary, TSC1 was found to show inhibitory activity toward human HSP70. Our result suggests that TSC1 (302-420 aa) shows differential interaction between the HSP70 homologues. This points toward the evolutionary significance of chaperoning system and the importance of eukaryotic tetratricopeptide repeat domain interaction motif -EEVD. Our study shows the evidence that TSC1 interacts with HSP70 and has a role to play in the chaperoning activity to maintain cellular homeostasis.

An Insight of Scientific Developments in TSC for Better Therapeutic Strategy.

Tuberous sclerosis complex (TSC) is a rare genetic disease, which is characterized by noncancerous tumors in multi-organ systems in the body. Mutations in the TSC1 or TSC2 genes are known to cause the disease. The resultant mutant proteins TSC1 (hamartin) and TSC2 (tuberin) complex evade its normal tumor suppressor function, which leads to abnormal cell growth and proliferation. Both TSC1 and TSC2 are involved in several protein-protein interactions, which play a significant role in maintaining cellular homeostasis. The recent biochemical, genetic, structural biology, clinical and drug discovery advancements on TSC give a useful insight into the disease as well as the molecular aspects of TSC1 and TSC2. The complex nature of TSC disease, a wide range of manifestations, mosaicism and several other factors limits the treatment choices. This review is a compilation of the course of TSC, starting from its discovery to the current findings that would take us a step ahead in finding a cure for TSC.

Characterization of P. aeruginosa Glucose 6- Phosphate Isomerase: A Functional Insight via In-Vitro Activity Study.

BACKGROUND: Glucose-6-phosphate isomerase (G6PI) catalyses the second step in glycolysis in the reversible interconversion of an aldohexose glucose 6-phosphate, a six membered ring moiety to a ketohexose, fructose 6-phosphate five membered ring moiety. This enzyme is of utmost importance due to its multifunctional role like neuroleukin, autocrine motility factor, etc. in various species. G6PI from Pseudomonas aeruginosa is less explored for its moonlighting properties. These properties can be predicted by studying the active site conservation of residues and their interaction with the specific ligand. METHODS: Here, we study the G6PI in a self-inducible construct in bacterial expression system with its purification using Ni-NTA chromatography. The secondary structure of pure G6PI is estimated using circular dichroism to further predict the proper folding form of the protein. The bioactivity of the purified enzyme is quantified using phosphoglucose isomerase colorimetric kit with a value of 12.5 mU/mL. Differential scanning fluorimetry and isothermal titration calorimetry were employed to monitor the interaction of G6PI with its competitive inhibitor, erythrose 4-phosphate and calculated the Tm, Kd and IC50 values. Further, the homology model for the protein was prepared to study the interaction with the erythrose 4-phosphate. MD simulation of the complex was performed at 100 ns to identify the binding interactions. RESULTS: We identified hydrogen bonds and water bridges dominating the interactions in the active site holding the protein and ligand with strong affinity. CONCLUSION: G6PI was successfully crystallized and data has been collected at 6Å. We are focused on improving the crystal quality for obtaining higher resolution data.

Structural and strategic landscape of PIKK protein family and their inhibitors: an overview.

Phosphatidylinositol-3 kinase-related kinases (PIKKs) is a class of six unique serine/threonine kinases that are characterized as high molecular mass colossal proteins present in multicellular organisms. They predominantly regulate the innumerable eukaryotic cellular processes, for instance, cell-signaling cascades related to DNA damage and repair, cell growth and proliferation, cell cycle arrest, genome surveillance, gene expression and many other important yet diverse functions. A characteristic PIKK member comprises of an N-terminal HEAT domain, followed by FAT domain, a highly conserved kinase catalytic domain, and a C-terminal FATC domain. In this comprehensive review, we reassess and discuss various established functions of all the six PIKK members with each function corroborated by their structural topology. In addition to the domain architecture of these atypical kinases, their specific inhibitors have been briefly deliberated. This review gives us the impression of the emergent importance of PIKKs, which, despite of their complexity, are the hub of research with respect to the inhibitor development.

High Yield Expression of Recombinant CD151 in E. coli and a Structural Insight into Cholesterol Binding Domain.

CD151 is an abundantly expressed eukaryotic transmembrane protein on the cell surface. It is involved in cell adhesion, angiogenesis and signal transduction as well in disease conditions such as cancer and viral infections. However, the molecular mechanism of CD151 activation is poorly understood due to the lack of structural information. By considering the difficulties in expressing the membrane protein in E. coli, herein we introduce the strategic design for the effective expression of recombinant CD151 protein in E. coli with high yield, that would aid for the structural studies. CD151 having four transmembrane domain (TMD's) along with small and a large extracellular loop (LEL) is constructed in parts to enhance the soluble expression of the protein attached with fusion tag. This has led to the high yield of the recombinant CD151 protein in the designed constructs. The recombinant CD151 protein is characterized and confirmed by western blot, CD and Mass peptide fingerprint. The molecular dynamics simulations (MDS) for the full-length CD151 shows conformational changes in the LEL of the protein in the presence and absence of cholesterol and indicate the certainty of closed and open conformation of CD151 based on cholesterol binding. The MDS results have led to the understanding of the possible underlying mechanism for the activation of the CD151 protein.

Tracing the GSAP-APP C-99 Interaction Site in the ß-Amyloid Pathway Leading to Alzheimer's Disease.

Gamma secretase activating protein (GSAP) present in ß-amyloid pathway orchestrates the formation of ß-amyloid plaques by γ-secretase activation and is an emerging therapeutic target for the treatment of Alzheimer's disease. It forms a ternary complex with γ-secretase and APP C-99. However, there are limited reports for the interaction of APP C-99 with GSAP. Here, we report the characterization of purified maltose binding protein (MBP) tagged human GSAP and its interaction with synthetic APP C-99 peptide fragments (712IATVIVITLVMLKKQ727 (712IQ727), 719TLVMLKKKQYTSIHHGVVEVDAAVT743 (719TT743) 734GVVEVDAAVTPEERHLSKMQQNGY757 (734GY757), and 746ERHLSKMQQNGYENPTYKFFEQMQN770 (746EN770)). The results emphasize the selective interaction of peptide (719TT743) with MBP-GSAP with a dissociation constant of 0.136 µM. Further, computational modeling of the GSAP-719TT743 complex finds an optimal bound pose of 719TT743 within an extended groove on the surface of GSAP. The preliminary results highlight the interaction between the two major proteins in the plausible ternary complex: APP C-99-GSAP-γ-secretase. It paves a futuristic path to investigate the GSAP-APP C-99 binding in detail and accentuates the role of GSAP in the ß-amyloid pathway.

Design, synthesis and biological evaluation of Helicobacter pylori inosine 5'-monophosphate dehydrogenase (HpIMPDH) inhibitors. Further optimization of selectivity towards HpIMPDH over human IMPDH2.

Inosine 5'-monophosphate dehydrogenase (IMPDH, EC 1.1.1.205) catalyzes a crucial step in guanine nucleotide biosynthesis, thereby governing cell proliferation. In contrast to mammalian IMPDHs, microbial IMPDHs are relatively less explored as potential targets for antimicrobial drug discovery. In continuation with our previous work, here we report the discovery of moderately potent and highly selective Helicobacter pylori IMPDH (HpIMPDH) inhibitors. The present study is mainly focused around our previously identified, modestly potent and relatively nonselective (for HpIMPDH over human IMPDH2) hit molecule IX (16i). In an attempt to optimize the selectivity for the bacterial enzyme, we screened a set of 48 redesigned new chemical entities (NCEs) belonging to 5-aminoisobenzofuran-1(3H)-one series for their in vitro HpIMPDH and human IMPDH2 inhibition. A total of 12 compounds (hits) demonstrated ≥70% HpIMPDH inhibition at 10 µM concentration; none of the hits were active against hIMPDH2. Compound 24 was found to be the most potent and selective molecule (HpIMPDH IC50 = 2.21 µM) in the series. The study reaffirmed the utility of 5-aminoisobenzofuran-1(3H)-one as a promising scaffold with great potential for further development of potent and selective HpIMPDH inhibitors.

Synthesis and In Vitro Enzymatic Studies of New 3-Aryldiazenyl Indoles as Promising Helicobacter pylori IMPDH Inhibitors.

BACKGROUND & OBJECTIVE: Helicobacter pylori infection is one of the primary causes of peptic ulcer followed by gastric cancer in the world population. Due to increased occurrences of multi-drug resistance to the currently available antibiotics, there is an urgent need for a new class of drugs against H. pylori. Inosine 5'-monophosphate dehydrogenase (IMPDH), a metabolic enzyme plays a significant role in cell proliferation and cell growth. It catalyses guanine nucleotide synthesis. IMPDH enzyme has been exploited as a target for antiviral, anticancer and immunosuppressive drugs. Recently, bacterial IMPDH has been studied as a potential target for treating bacterial infections. Differences in the structural and kinetic parameters of the eukaryotic and prokaryotic IMPDH make it possible to target bacterial enzyme selectively. METHODS: In the current work, we have synthesised and studied the effect of substituted 3-aryldiazenyl indoles on Helicobacter pylori IMPDH (HpIMPDH) activity. The synthesised molecules were examined for their inhibitory potential against recombinant HpIMPDH. RESULTS: In this study, compounds 1 and 2 were found to be the most potent inhibitors amongst the database with IC50 of 0.8 ± 0.02µM and 1 ± 0.03 µM, respectively. CONCLUSION: When compared to the most potent known HpIMPDH inhibitor molecule C91, 1 was only four-fold less potent and can be a good lead for further development of selective and potent inhibitors of HpIMPDH.

Identification of selective inhibitors of Helicobacter pylori IMPDH as a targeted therapy for the infection.

Helicobacter pylori (H. pylori), the major cause of several gastric disorders has been recognied as a type I carcinogen. By virtue of resistance developed by H. pylori strains, currently used antibiotic based treatments rather demonstrate high failure rates. Hence, there is an emerging need for identification of new targets to treat H. pylori infection. Inosine-5'-monophosphate dehydrogenase (IMPDH) has been studied as a potential target to treat H. pylori infection. Here, a detailed enzyme kinetic study of recombinant expressed H. pylori inosine-5'-monophosphate dehydrogenase (HpIMPDH) is presented. A new in-house synthesized indole-based scaffold is identified as an inhibitor for HpIMPDH. These indole-based compounds showed non-competitive inhibition against IMP and NAD+ whereas the benzimidazole compounds were found be uncompetitive inhibitors. The new indole scaffold ensures specificity due to its high selectivity for bacterial IMPDH over human IMPDH II. Our work aims to overcome the drawback of existing inhibitors by introducing new indole scaffold for targeting bacterial IMPDH.

One- and Two-Component Organogels Containing Cyanostilbene without any Auxiliary Substituents.

Pyridyl acrylonitrile without traditional auxiliary groups form stable organogels in ethanol. The addition of a second non-gelating cyanostilbene component results in a more stable two-component gel. Single crystal X-ray data reveal the influence of C-H⋅ ⋅ ⋅N, C-H⋅ ⋅ ⋅π, and π-π interactions in the formation of organogels. The morphology of the xerogels was studied by using SEM, which showed the self-assembly of molecules to fibers and sheet-like structures, and phase differences upon the gel formation and the structural phase characterization was measured using powder XRD. Exposure of the organogels to acidic (TFA) vapors results in distinct color changes and loss of gelation properties, thus highlighting the potential of these gels in sensing. The results represent a rare example of two-component organogels using two different cyanostilbene units and show that functional two-component organogels can be formed by utilizing the synergistic effects of the individual components.