Microwave-induced one-pot synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole hybrids as antiproliferative agents and density functional theory study.

Herein, we outline a highly efficient PEG-4000-mediated one-pot three-component reaction for the synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole derivatives (5a-r) at up to 96% yield as antiproliferative agents. This three-component protocol offers the advantages of an environmentally benign reaction, excellent yield, quick response time, and operational simplicity triggered by the copper catalyst under microwave irradiation. All the synthesized compounds were tested for antiproliferative activity against six human solid tumor cell lines, that is, A549 and SW1573 (nonsmall cell lung), HBL100 and T-47D (breast), HeLa (cervix), and WiDr (colon). Among them, six compounds, 5g-j, 5m, and 5p, demonstrated effective antiproliferative action with GI50 values under 10 µM. Furthermore, density functional theory (DFT) calculations were performed for all the synthesized molecules through geometry optimizations, frontier molecular orbital approach, and molecular electrostatic potential (MESP). The theoretical DFT calculation was performed using the DFT/B3LYP/6-31+G (d,p) basis set. Moreover, the biological reactivity of all the representative synthesized molecules was compared with the theoretically calculated quantum chemical descriptors and MESP 3D plots. We also investigated the drug-likeness characteristic and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction. In general, our approach enables environmentally friendly access to 3-imidazolyl indole clubbed 1,2,3-triazole derivatives as prospective antiproliferative agents.

Ultrasound-promoted convenient and ionic liquid [BMIM]BF4 assisted green synthesis of diversely functionalized pyrazolo quinoline core via one-pot multicomponent reaction, DFT study and pharmacological evaluation.

An ultrasound-assisted green protocol for one-pot synthesis of a new series of pharmaceutically relevant pyrazolo quinoline derivatives (4a-t) were synthesized, characterized, and evaluated using DFT and biological activities. Pyrazolo quinoline derivatives (4a-t) were synthesized via a three-component tandem reaction of 1,3-dicarbonyl compound (1a-b), substituted aromatic aldehyde (2a-o), and 5-amino indazole (3a) in the presence of 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM]BF4 ionic liquid in ethanol at ambient conditions. The main purpose of the present work is selective functionalization of pyrazolo quinoline (4a-t) core excluding another potential parallel reaction under environmentally benign reaction conditions. The present protocol shows features such as amphiphilic behavior of ionic liquid during reaction transformation, and reusability of the [BMIM]BF4 ionic liquid under mild reaction condition. All newly derived compounds were evaluated for their in vitro anti-inflammatory and antioxidant activity. Among them, compound 4c showed encouraging antioxidant activity compared with standard antioxidant ascorbic acid, and compounds 4n and 4r displayed very good anti-inflammatory activity compared with a standard drug. In this study, a theoretical computational density functional study was also executed to perform the geometry optimizations, frontier molecular orbital approach, and molecular electrostatic potential (MESP). The DFT study was carried out with the basis set DFT/B3LYP/6-31+G (d, p) level of theory. The quantum chemical descriptors (QCDS) and MESP diagrams were plotted to examine the biological reactivities of representative pyrazolo quinolines (4a-t).

A multicentric study on dermoscopic patterns and clinical-dermoscopic-histological correlates of basal cell carcinoma in Indian skin.

BACKGROUND: Literature on the dermoscopic patterns of basal cell carcinoma (BCC) in India is limited. AIM: To describe the dermoscopic pattern and dermoscopic-histopathological correlation in a large cohort of patients with BCC from India, with a particular focus on skin of colour (SOC). METHODS: This retrospective study was conducted under the aegis of the Dermatoscopy Society of India. Clinical details were collected, and two lead authors independently analysed dermoscopic images of BCC for a predefined set of characteristics. Histopathological slides/blocks were reviewed, and dermoscopic-histological correlation attempted. RESULTS: In total, 143 patients with BCC and skin phototypes IV-VI were included. The mean largest BCC diameter was 3.10 ± 3.68 cm and there was a significant but weak association between duration and largest dimension of the lesion (Spearman ρ = 0.33, P < 0.01). Nearly half of the cases were diagnosed with pigmented BCC and the most common histological subtype was nodular BCC (37.9%). Dermoscopically, blue-grey dots and arborizing vessels were the most common features (60.0%). Pigmentary changes were found in the majority of cases, and included blue-white veil, blue-grey ovoid nests and maple leaf-like areas. A third of our patients had short linear telangiectasia, polymorphic vessels and regular dotted vessels, and another third exhibited a dermoscopic rainbow effect. Arborizing vessels were significantly more common with micronodular (78.9%) and nodular variants (74.1%, P = 0.05), whereas regular dotted vessels (68.4%, P = 0.04), blue-white veil (84.2%, P = 0.02) were significantly associated with micronodular variant. CONCLUSION: The dermoscopic patterns of blue-white veil and regular dotted vessels are indicators towards micronodular BCC in SOC and can help in prioritizing treatment.

Octupolar Cyclotriphosphazene-Cored Self-Standing Covalent Organic Framework Membranes as Nonlinear Optical Materials: Impact of Linkage Types and Material Forms.

Conjugated and processable self-standing vinylene-linked covalent organic framework membranes (COFMs) are highly demanding for photonics and optoelectronics. In this work, we have fabricated the first cyclotriphosphazene (CTP) cored vinylene-linked self-standing COFM (CTP-PDAN). For comparison purposes, we have successfully fabricated the imine-linked congener (CTP-PDA). Leveraging the inherent nonlinear optical (NLO) response of the CTP core, both membranes were directly mounted to evaluate NLO parameters using the open-aperture (OA) Z-scan technique. Direct measurement of NLO responses on membranes is advantageous and free from solvent and scattering effects, making it a more practical approach compared to the conventional dispersion mode. The OA Z-scan transmission yields a reverse saturable absorption signature exhibiting a higher NLO absorption coefficient (ß) of 58.37 cm/GW for CTP-PDAN, compared to that of the imine-linked CTP-PDA COFM (ß = 8.5 cm/GW). These results can be correlated to the efficient conjugation through the vinylene linkage in CTP-PDAN compared to the imine linked congener.

Terahertz Conductivity of Free-Standing 3D Covalent Organic Framework Membranes Fabricated via Triple-Layer-Dual Interfacial Approach.

Processable covalent organic framework membranes (COFM) are emerging as potential semiconducting materials for device applications. Nevertheless, the fabrication of crystalline and free-standing 3D COFMs is challenging. In this work, a unique time and solvent-efficient triple-layer-dual interfacial (TLDI) approach for the simultaneous synthesis of two 3D COFMs from a single system is developed. Besides, for the first time, the optical conductivity of these free-standing 3D COFMs is analyzed using terahertz (THz) spectroscopy in transmission mode. Interestingly, these membranes show excellent transmittance at THz frequencies with very high intrinsic THz conductivities. The evaluated scattering time and plasma frequency of the free carriers of the COFMs are highly promising for future applications in optoelectronic devices in THz frequencies.

Meglumine-based Sustainable Three-component Deep Eutectic Solvent Applicable for the Synthesis of Pyrazolo[5,1-b]quinazoline-3-carboxylates as a Sensing Probe for Cu2+ Ions.

An unprecedented meglumine-based three-component deep eutectic solvent (3c-DES) (MegPAc) was synthesized using meglumine, p-toluenesulfonic acid (PTSA), and acetic acid as a renewable, and non-toxic solvent. The exploitation of the MegPAc as an eco-friendly reaction media to construct a selective and sensitive small organic molecular sensing probe, namely, pyrazolo[5,1-b]quinazoline-3-carboxylates (PQCs) was executed. Captivatingly, the MegPAc served the dual role of solvent and catalyst, and it delivered the title components with 69-94 % yields within 67-150 minutes. Furthermore, a UV-visible study unfolds the selective detection of Cu2+ ions with our synthetic probe 4 ba and resulted in hypsochromic shift due to electrostatic interactions. Additionally, 1H NMR titration study and density functional theory (DFT) calculations were performed to attest the binding mechanism of sensing probe 4 ba and Cu2+ ions. Worthy of mention, this protocol unveils the efficacy of meglumine-based 3c-DES for the first time as a bio-renewable system to synthesize the PQCs.

A Prospective, Nonrandomized, Open-label Study, Comparing the Efficacy, Safety, and Tolerability of Fractional CO2 Laser versus Fractional Microneedling Radio Frequency in Acne Scars.

BACKGROUND: Acne scar is a distressing psychosocial problem, and it has a negative effect on the quality of life. Although variety of approaches are available, demand of less invasive and more effective ways for their treatment is needed. OBJECTIVE: This study aimed to assess and compare the clinical safety, efficacy, and tolerability of fractional carbon dioxide (FCO2) laser versus fractional microneedling radio frequency (MNRF) in the management of acne scars. MATERIALS AND METHODS: This study was a prospective, observational, nonrandomized, open-labeled study of total 50 patients selected according to Goodman and Baron global qualitative acne scar grading, and they were divided into two groups of 25 each, having Fitzpatrick skin type III-V. A total of four sessions were given for both the groups at an interval of 2 months. The assessment was done by the treating physician as well as by the blinded physician. Both the subjective and the objective assessment was done at the last follow up given at second month of the fourth session. RESULTS: The mean score of 25 patients in each group of FCO2 and fractional MNRF, decreased from 29.24 to 10.7 (i.e., 63.41%) and from 33.24 to 13.04 (i.e., 60.72%), respectively, as calculated by Goodman and Baron quantitative grading assessed by the treating physician (P = 0.0001). Grade 4 (>75%) improvement was shown by four patients and Grade 3 improvement (51%-75%) was shown by 14 patients among FCO2 group, and similarly Grade 4 (>75%) improvement was shown by three patients and Grade 3 improvement (51%-75%) was shown by 12 patients among MNRF group, as observed by a blinded physician (P = 0.689). CONCLUSION: Both modalities are equally effective in the treatment of acne scars; however, fractional MNRF having lesser down time and Post inflammatory hyperpigmentation (PIH) among darker skin shades, with good patient satisfaction score, makes it an efficient and safer treatment option as compared to FCO2.

Nail Changes in Leprosy: An Observational Study of 125 Patients.

INTRODUCTION: Leprosy is a disease primarily affecting skin and nerve. Nail involvement, although indirect, is observed in several patients. This is a study to determine the pattern of nail changes in leprosy. METHODS: It was an observational study involving 125 patients. Apart from cutaneous and neurological examination, nails were examined. Diagnosis was confirmed by previous records in already diagnosed cases, while by slit skin smear and histopathologically in new cases. Patients were grouped as per Ridley-Jopling classification and further subdivided as per age, sex, and duration and reaction status. Nail changes in these groups were summarized and compared. RESULTS: Overall prevalence of nail changes was 80% with 66.6% in TT patients, 79.4% in BT patients 50% in BB patients, 83.7% in BL patients and 84.3% in LL patients. Longitudinal melanonychia and longitudinal ridges were frequent finger nail changes with longitudinal melanonychia being more common among tuberculoid pole and longitudinal ridges among lepromatous pole. Brachyonychia, subungual hyperkeratosis and brown black pigmentation were frequent finger nail changes, with onychorrhexis being commonest among TT patients, subungual hyperkeratosis among BT patients, while brachyonychia among BL and LL patients. Anonychia and rudimentary nails were not found in tuberculoid pole. Beau's lines, terry nails, pterygium, pincer nail, and onychorrhexis were significantly more frequent in ENL patients. Onychomadesis, which is not reported yet in leprosy, was found in one patient after severe ENL. CONCLUSION: Various changes in leprosy are due to multiple causes like neuropathic, traumatic, vascular, osseous, infections and drugs reflecting extensive systemic morbidity caused by Mycobacterium leprae.

Paraneoplastic Eosinophilic Dermatosis in a Case of Chronic Lymphocytic Leukemia.

Eosinophilic dermatosis of hematologic malignancy is a rare paraneoplastic manifestation particularly associated with chronic lymphocytic leukemia (CLL).Clinically, it presents as a peculiar polymorphic pruritic eruption with characteristic histological findings of superficial and deep dense perivascular infiltrate of lymphocytes and eosinophils without any vasculitis. Although it has been reported intermittently with different names, there is paucity of reports of this condition in Indian literature. Here, we report a patient of CLL having insect bite-like eruptions nonresponsive to conventional therapy and confirmed as eosinophilic dermatosis on histology. Patient was having eruptions well before the diagnosis of malignancy, and intensity as well as frequency increased as the disease progressed. Good control over the disease was achieved using chemotherapy and steroids. Thus, this case explains diagnostic and prognostic significance of eosinophilic dermatosis in CLL.

Localized Cutaneous Hyalohyphomycosis by Fusarium spp. Over a Postsurgical Scar: Response to Fluconazole.

Hyalohyphomycosis are opportunistic fungal infections caused by fungi with colorless septate hyphae. Fusarium is a hyalohyphomycetes which can cause localized or disseminated infections depending on host immunity. Our patient had an infectious lesion over the coronary artery bypass grafting (CABG) scar which was not responding to antibacterial treatment. Further investigations revealed it to be localized cutaneous Fusarium infection. The patient was treated with fluconazole 3 mg/kg/day for 3 weeks and responded very well without any recurrence during the next 3 months follow-up. Thus, this case highlights the effectiveness of fluconazole in uncommon fungal infection.