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Type 2 diabetes mellitus is a long-term medical illness in which the body either becomes resistant to insulin or fails to produce it sufficiently. Mostly, combinatorial therapy is required to control blood glucose levels. However, combinatorial therapy has detrimental side effects. The prevalence of the cases and subsequent increases in medical costs of the same intimidate human health globally. While there have been a lot of studies focused on developing diabetic regimens that work to lower blood glucose levels, their effectiveness is short-lived because of unfavorable side effects, such as weight gain and hypoglycemia. In recent years, the PIN1 (protein interacting with NIMA) enzyme has attracted the attention of researchers. Previous studies suggested that PIN1 may act on the various substrates that are involved in the progression of T2DM and also help in the management of diabetes-related disorders. Thus, the focus of the current review is to examine the correlation between PIN1, T2DM and its related disorders and explore the possibility of developing novel therapeutic targets through PIN1 inhibition.

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Poly cystic ovary syndrome (PCOS) is considered as one of the common hormonal disorders affecting 6-20% of women in their reproductive age with characteristic features include anovulatory infertility, hyperandrogenism, cystic follicles and insulin resistance. The gene CYP play an important role in pathophysiology of hyperandrogenism associated with PCOS. An elevated androgens are reported in PCOS condition due to overexpression of the enzyme CYP450 17 α: . As well as diminished levels of aromatase (CYP450 19) were observed in several hyperandrogenic PCOS patients. The powdered leafy material of Cinnamomum malabatrum was subjected to Soxhlet extraction. The plant extract was subjected to Gas chromatography-MS analysis (GC-MS), and the chromatogram obtained revealed the presence of active chemical constituents like 1(10),9(11)-B-Homolanistadiene for the first time and other potential compounds. Hypothesis has raised to interpret the efficiency of phytoconstituents of Cinnamomum malabatrum on these enzyme targets and which may be a novel drug candidate for the treatment and maintenance of hyperandrogenism associated with PCOS. Thus, the results obtained from the in-silico study of Cinnamomum malabatrum leaf extract using computational approaches indicate that the phytoconstituents have good affinities for the selected two key targets. ADME and PASS studies has been performed for active phytoconstituents homolanistadiene, ß-sitosterol, cycloartenol and a pyrazole derivative, and results revealed the Lipinski drug-likeness and pharmacological potential. In conclusion, this work throws a new insight into the possibility of the active phytoconstituents on binding the two active CYP45017 α and CYP45019 aromatase enzymes which facilitates development of novel compounds for hyperandrogenism associated with PCOS.

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Drug repositioning offers two main advantages in drug discovery - the process is less tedious and less costly. In the past, many drugs like thalidomide and sildenafil were successfully repositioned but the process was entirely serendipitous. These days drug repositioning is widely accepted as an alternate method of drug discovery and the process is based on building a strong hypothesis guided by systematic computational and experimental methods. One of the methods used in drug repositioning is based on shared side effects by drugs of different pharmacological categories. This method rests on the principle that drugs that share side effects might also share common biological targets and therefore same pharmacological indications. Old drugs can be repositioned for new uses by identifying the shared side effects of existing drugs and by modulating their chemical structure if required. Breast cancer is the most common type of cancer in women and the second leading cause of death worldwide after lung cancer in both men and women. Letrozole, an aromatase inhibitor, is used in the treatment of advanced, recurrent and metastatic breast cancer in post-menopausal women. Identification of drugs that share side effects with letrozole might help us to identify a potential drug for repositioning in the treatment of breast cancer. Ropinirole, a dopaminergic agonist was found to share the maximum number of side effects with letrozole. Studies have proposed that dopaminergic agonists induce apoptosis in breast, colon, ovarian cancer cells and leukemia neuroblastoma. This is consistent with our hypothesis that ropinirole that shares the maximum number of side effects with letrozole might be effective in the management of breast cancer. This hypothesis was further validated by preliminary molecular docking and in-vitro cell-line studies.

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A 70-year-old female patient presented with proptosis of right eye for the past 15 days and defective vision in both eyes since birth. She was found to have eccentric painful proptosis of right eye along with features of oculocutaneous albinism. Eccentric proptosis was due to an orbital mass which proved to be a plexiform neurofibroma by histopathological examination. The case is presented for its rarity, as an isolated orbital plexiform neurofibroma without the systemic features of neurofibromatosis is rare and its coincidental presentation with oculocutaneous albinism is yet rare and has not been reported so far.

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Inclusion complex formation of two local anesthetics drugs (lidocaine (LC) and prilocaine (PC)) with α- and ß-cyclodextrins (CDs) in aqueous solution were studied by absorption, fluorescence, time-resolved fluorescence and molecular modeling methods. The formation of inclusion complexes was confirmed by 1H NMR, FTIR, differential scanning calorimetry, SEM, TEM and X-ray diffractometry. Both drugs formed 1:1 inclusion complex and exhibit biexponential decay in water whereas triexponential decay in the CD solution. Nanosized self-aggregated particles of drug: CD complexes were found by TEM. Both experimental and theoretical studies revealed that the phenyl ring with the amide group of the drug is encapsulated in the hydrophobic CD nanocavity. Investigations of energetic and thermodynamic properties confirmed the stability of the inclusion complexes. van der Waals interactions are mainly responsible for enthalpy driven complex formation of LC and PC with CDs.

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Sulfadiazine (SDA) and sulfisomidine (SFM) inclusion complexes with two cyclodextrins (α-CD and ß-CD) are studied in aqueous as well as in solid state. The inclusion complexes are characterized by UV-visible, fluorescence, time correlated single photon counting, FTIR, DSC, PXRD and (1)H NMR techniques. The self assembled SDA/CD and SFM/CD inclusion complexes form different types of nano and microstructures. The self assembled nanoparticle morphologies are studied using SEM and TEM techniques. SDA/α-CD complex is formed hierarchal morphology, SDA/ß-CD and SFM/ß-CD complexes form the nanosheet self assembly. However, SFM/α-CD complex forms nanoporous sheet self assembly. van der Waals, hydrophobic and hydrogen bonding interaction play a vital role in the self assembling process.

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Cyclodextrin (α and ß) based nanostructures formed with 2-aminobenzophenone, 3-aminobenzophenone through the supramolecular self assembly are studied by absorption, fluorescence, time-resolved fluorescence, SEM, TEM, FT-IR, DSC, PXRD and (1)H NMR. The unequal layer by layer nanosheets and nanoribbons are formed through self assembly of 3ABP/CD inclusion complexes. 2ABP/α-CD complex nanostructures show the self assembly hierarchical thread structure and ß-CD complexes displays a nanobrick structure. The formation of nanostructures are prearranged to HO⋯H, NH2⋯O and H2N⋯H intermolecular hydrogen bond between individual complexes. The absorption and fluorescence spectral changes explicit formation of 1:1 inclusion complexes and solvent study demonstrate the ESIPT and TICT present in both molecules. The thermodynamic parameters (ΔH, ΔG and ΔS) of 2ABP and 3ABP molecule and the inclusion complexes were determined from semiempirical PM3 calculations.

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Inclusion complex formation of isoprenaline (ISOP) and methyldopa (MDOP) with α-CD and ß-CD were investigated. Solid inclusion complex nanomaterials were characterized by SEM, TEM, FTIR, DSC, (1)H NMR and XRD methods. Spectral results showed that single emission (monomer) noticed in aqueous solution where as dual emission (excimer) in CD. Both drugs formed 1:2 (CD-drug2) inclusion complexes with CDs. Time-resolved fluorescence studies show that single exponential decay observed in water whereas biexponential decay observed in CD. Nano-sized particles were found in ISOP/CD while vesicles were obtained in MDOP/CD complexes. DSC results revealed that the thermal stability of drugs was improved when it was included in the CD nanocavity. Based on PM3 calculations, the inclusion structure of ISOP/CD and MDOP/CD complexes were proposed. Thermodynamic parameters and binding affinity of complexation of CD were determined by PM3 method.

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The absorption and fluorescence spectra of three Carboxamides namely (E)-2-(4-Chlorobenzylideneamino)-N-(2-chlorophenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (C(1)), (E)-N-(3-Chlorophenyl)-2-(3, 4-dimethoxybenzylideneamino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (C(2)) and (E)-N-(3-Chlorophenyl)-2-(3,4,5-trimethoxybenzylideneamino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (C(3)) have been recorded at room temperature in solvents of different polarities using dielectric constant (ε) and refractive index (n). Experimental ground (µ(g)) and excited (µ(e)) state dipole moments are estimated by means of solvatochromic shift method and also the excited dipole moments are estimated in combination with ground state dipole moments. It was estimated that dipole moments of the excited state were higher than those of the ground state of all three molecules. Further, the changes in dipole moment (Δµ) were calculated both from solvatochromic shift method and on the basis of microscopic empirical solvent polarity parameter (E(N)(T)) and the values are compared.

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The title compound, C24H24N2O3S, exhibits antifungal and antibacterial properties. The compound crystallizes with two molecules in the asymmetric unit, with one molecule exhibiting 'orientational disorder' in the crystal structure with respect to the cyclohexene ring. The o-toluidine groups in both molecules are noncoplanar with the respective cyclohexene-fused thiophene ring. In both molecules, there is an intramolecular N-H...N hydrogen bond forming a pseudo-six-membered ring which locks the molecular conformation and eliminates conformational flexibility. The crystal structure is stabilized by O-H...O hydrogen bonds; both molecules in the asymmetric unit form independent chains, each such chain consisting of alternating 'ordered' and 'disordered' molecules in the crystal lattice.

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The molecular structure of the title compound, C(24)H(25)N(3)O(2)S, is stabilized by intra-molecular N-H⋯N, C-H⋯O and C-H⋯S hydrogen bonds. There are no significant inter-molecular inter-actions.

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In the title compound, C(14)H(16)N(2)O(2)S, the two aromatic rings make a dihedral angle of 13.9 (1)°. The crystal structure is stabilized by both inter- and intra-molecular N-H⋯O, C-H⋯O and C-H⋯N hydrogen bonds.

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The title compounds, both C(23)H(21)ClN(2)OS, are isomeric, with (I) and (II) being the N-3-methylphenyl and N-2-methylphenyl derivatives, respectively. The dihedral angle between the 4-chlorophenyl group and the thiophene ring in (II) [38.1 (1) degrees ] is larger than that in (I) [7.1 (1) degrees ], indicating steric repulsion between the chlorophenyl and o-toluidine groups in (II). In both compounds, an intramolecular N-H...N hydrogen bond forms a pseudo-six-membered ring, thus locking the molecular conformation. In the crystal structures, molecules are connected via N-H...O hydrogen bonds, forming chains along the b axis in (I) and along the c axis in (II). Intermolecular C-H...O/S and pi-pi interactions are also observed in (II), but not in (I).

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The compounds 2-[[(E)-(4-methoxyphenyl)methylene]amino]-N-(3-methylphenyl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide, C24H24N2O2S, (I), and N-(4-methylphenyl)-2-[[(E)-(4-methylphenyl)methylene]amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide, C24H24N2OS, (II), show antibacterial and antifungal activities. The m-toluidine ring in (I) and the p-toluidine ring in (II) are coplanar with their respective thiophene rings. In (I), an intermolecular C-H...O hydrogen bond is present, whereas (II) does not exhibit any significant intermolecular interactions. However, in both compounds, an intramolecular N-H.N hydrogen bond forms a pseudo-six-membered ring, thus locking the molecular conformation and eliminating conformational flexibility.

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The two title compounds, 2-([(1Z)-[4-(dimethylamino)phenyl]methylene]amino)-4,5-dimethyl-N-(2-methylphenyl)thiophene-3-carboxamide, C(23)H(25)N(3)OS, (I), and 2-([(1E)-[4-(dimethylamino)phenyl]methylene]amino)-N-(4-methylphenyl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide,C(25)H(27)N(3)OS, (II), show antibacterial and antifungal activities. The asymmetric unit of (II) contains two crystallographically independent molecules. The o-toluidine ring in (I) lies gauche with respect to the thiophene ring. In (II), the p-toluidine ring is coplanar with the thiophene ring in one molecule, but is tilted from it in the other molecule. Neither structure exhibits any significant intermolecular interactions, but in both, an intramolecular N-H.N hydrogen bond forms a pseudo-six-membered ring, thus locking the molecular conformation and removing conformational flexibility.

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