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1.
Article in English | MEDLINE | ID: mdl-39011620

ABSTRACT

ABSTRACT: Adrenocortical carcinoma is a rare malignancy and even rarer in infancy. Most of these tumors in the pediatric age group are hormonally active and predominantly present with virilization. We report a case of a 1-year-3-month-old female child presenting with virilization. She presented with hypertension, hypertrichosis, clitoromegaly (virilization), and elevation of plasma testosterone and dehydroepiandrosterone. A discussion of this case and a review of the literature on this entity are presented.

2.
Bioorg Med Chem ; 109: 117799, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38897138

ABSTRACT

Natural products as starting templates have shown historically major contribution to development of drugs. Inspired by the structure-function of an anticancer natural alkaloid Rutaecarpine, the Scaffold-hopped Acyclic Analogues of Rutaecarpine (SAAR) with 'N'-atom switch (1°-hop) and ring-opening (2°-hop) were investigated. A new synthetic route was developed for an effective access to the analogues, i.e. 2-indolyl-pyrido[1,2-a]pyrimidinones, which involved preparation of N-Boc-N'-phthaloyltryptamine/mexamine-bromides and pyridopyrmidinon-2-yl triflate, a nickel/palladium-catalysed Ullmann cross-coupling of these bromides and triflate, deprotection of phthalimide followed by N-aroylation, and Boc-deprotection. Fourteen novel SAAR-compounds were prepared, and they showed characteristic antiproliferative activity against various cancer cells. Three most active compounds (11a, 11b, and 11c) exhibited good antiproliferative activity, IC50 7.7-15.8 µM against human breast adenocarcinoma cells (MCF-7), lung cancer cells (A549), and colon cancer cells (HCT-116). The antiproliferative property was also observed in the colony formation assay. The SAAR compound 11b was found to have superior potency than original natural product Rutaecarpine and an anticancer drug 5-FU in antiproliferative activities with relatively lower cytotoxicity towards normal breast epithelial cells (MCF10A) and significantly higher inhibitory effect on cancer cells' migration. The compound 11b was found to possess favourable in silico physicochemical characteristics (lipophilicity-MLOGP, TPSA, and water solubility-ESOL, and others), bioavailability score, and pharmacokinetic properties (GI absorption, BBB non-permeant, P-gp, and CYP2D6). Interestingly, the compound 11b did not show any medicinal chemistry structural alert of PAINS and Brenk filter. The study represents for the first time the successful discovery of new potent anticancer chemotypes using Rutaecarpine natural alkaloid as starting template and reaffirms the significance of natural product-inspired scaffold-hopping technique in drug discovery research.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Drug Screening Assays, Antitumor , Indole Alkaloids , Quinazolines , Humans , Quinazolines/chemistry , Quinazolines/pharmacology , Quinazolines/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Indole Alkaloids/chemistry , Indole Alkaloids/pharmacology , Indole Alkaloids/chemical synthesis , Cell Proliferation/drug effects , Structure-Activity Relationship , Molecular Structure , Cell Line, Tumor , Pyrimidinones/chemistry , Pyrimidinones/pharmacology , Pyrimidinones/chemical synthesis , Indoles/chemistry , Indoles/pharmacology , Indoles/chemical synthesis , Dose-Response Relationship, Drug , Quinazolinones
3.
RSC Med Chem ; 15(3): 937-962, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38516586

ABSTRACT

DNA polymerase ß (Polß) is crucial for the base excision repair (BER) pathway of DNA damage repair and is an attractive target for suppressing tumorigenesis as well as chemotherapeutic intervention of cancer. In this study, a unique strategy of scaffold-hopping-based molecular editing of a bioactive agent NSC-666719 was investigated, which led to the development of new molecular motifs with Polß inhibitory activity. NSC compound and its analogs (two series) were prepared, focusing on pharmacophore-based molecular diversity. Most compounds showed higher activities than the parent NSC-666719 and exhibited effects on apoptosis. The inhibitory activity of Polß was evaluated in both in vitro reconstituted and in vivo intact cell systems. Compound 10e demonstrated significant Polß interaction and inhibition characteristics, including direct, non-covalent, reversible, and comparable binding affinity. The investigated approach is useful, and the discovered novel analogs have a high potential for developing as anticancer therapeutics.

4.
Heliyon ; 10(3): e24588, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38322968

ABSTRACT

The organofluorine hexahydropyrimidine derivatives are used in the drug discovery due to its steric nature to hydrogen and its extreme electronegativity. The Ethyl 5-hydroxy-2-thioxo-4-(p-tolyl)-6-(trifluoromethyl)hexahydropyrimidine-5-carboxylate (ETP5C) compound was synthesized and characterized by NMR (13C and 1H), FT-IR and UV-Vis spectroscopic techniques for experimentally and theoretically and elemental analyses, mass spectra also investigated. The most stable structure of synthesized molecule was studied by PES analysis in gas and liquid medium. The structural parameters such as bond length and bond angle of the title molecule have been obtained by DFT/B3LYP/6-311++G (d,p) set and compared with the structurally related experimental data of the compounds. The π-to-π* transition of the ETP5C molecule is identified using UV-Vis absorption spectral analysis. In addition, the chemical stability and reactivity are investigated using HOMO-LUMO analysis. The minimal HOMO-LUMO energy gap (4.6255 eV) clearly explains that the ETP5C molecule is more reactive for receptors. The nucleophilic and electrophilic regions such as active sites have been shown by MEP, ELF, LOL and Fukui functions. The second order optical effect has been explained by NLO analysis. The docking was performed with antineoplastic proteins that exhibit against the development of tumor cells.

5.
ChemMedChem ; 19(1): e202300562, 2024 01 02.
Article in English | MEDLINE | ID: mdl-37975190

ABSTRACT

An approach of natural product-inspired strategy and incorporation of an NP-privileged motif has been investigated for the discovery of new tubulin polymerization inhibitors. Two series, N-Arylsulfonyl-3-arylamino-5-amino-1,2,4-triazole derivatives, and their isomers were considered. The compounds were synthesized by construction of the N-aryl-1,2,4-triazole-3,5-diamine motif and sulfonylation. Although the chemo- and regioselectivity in sulfonylation were challenging due to multiple ring-tautomerizable-NH and exocyclic NH2 functionalities present in the molecular motifs, the developed synthetic method enabled the preparation of designed molecular skeletons with biologically important motifs. The approach also led to explore interesting molecular regio- and stereochemical aspects valuable for activity. The X-ray crystallography study indicated that the hydrogen bonding between the arylamine-NH and the arylsulfonyl-"O" unit and appropriate molecular-functionality topology allowed the cis-locking of two aryls, which is important for tubulin-binding and antiproliferative properties. All synthesized compounds majorly showed characteristic antiproliferative effects in breast cancer cells (MCF-7), and four compounds exhibited potent antiproliferative activity. One compound potently bound to tubulin at the colchicine site and inhibited tubulin polymerization in vitro. The compound significantly depolymerized microtubules in MCF-7 cells, arrested the cells at the G2/M phase, and induced cell death. This study represents the importance of the design strategy in medicinal chemistry and the molecular structural features relevant to anticancer anti-tubulin properties. The explored molecules have the potential for further development.


Subject(s)
Antineoplastic Agents , Tubulin Modulators , Humans , Tubulin Modulators/chemistry , Structure-Activity Relationship , Tubulin/metabolism , Cell Proliferation , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Polymerization , Drug Screening Assays, Antitumor , Molecular Structure
6.
Drug Discov Today ; 29(1): 103845, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38013043

ABSTRACT

In both academia and the pharmaceutical industry, innovative hypotheses, methodologies and technologies that can shorten the drug research and development, leading to higher success rates, are vital. In this review, we demonstrate how innovative variations of the scaffold-hopping strategy have been used to create new druggable molecular spaces, drugs, clinical candidates, preclinical candidates, and bioactive agents. We also analyze molecular modulations that enabled improvements of the pharmacodynamic (PD), physiochemical, and pharmacokinetic (PK) properties (P3 properties) of the drugs resulting from these scaffold-hopping strategies.


Subject(s)
Drug Discovery , Drug Industry , Drug Discovery/methods , Drug Industry/methods , Drug Design
7.
J Cancer Res Ther ; 19(5): 1098-1102, 2023.
Article in English | MEDLINE | ID: mdl-37787269

ABSTRACT

Pilomatrix carcinoma is a rare tumor arising from the hair follicle matrix cells most commonly seen in the head and neck region. Also known as "calcified epithelial carcinoma of Melherbe," it was first reported in 1980 by Lopansri and Mihm. Since then till date to the best of our knowledge only around 125 cases were reported in literature, of which only 11 cases were reported to arise from histologically proven areas of previous pilomatrixoma which is the benign variant. One such case is being reported here along with the review of literature. A 50-year-old man presented with a swelling in the nape of his neck since 6 months, which was gradually increasing in size. He had a history of similar swelling at the same site 18 months back for which he underwent a surgery at a center outside. Final histopathology report was suggestive of pilomatrixoma with negative margin. Wide local excision of the tumor with 3 cm margin, placement of surgical clips followed by a primary closure was done. The final histopathology report is suggestive of pilomatrix carcinoma. The patient has no recurrence in 6 months follow-up. The differential diagnosis of pilomatrix carcinoma should be considered in cases of recurrent skin tumors. Wide local excision is the preferred treatment. Re-excision should be done in margin positive cases and cases where simple excision was done due to improper preoperative diagnosis. Due to the rarity of the disease, adjuvant treatment is not properly defined.


Subject(s)
Bone Neoplasms , Breast Neoplasms , Carcinoma , Hair Diseases , Pilomatrixoma , Skin Neoplasms , Male , Humans , Middle Aged , Pilomatrixoma/diagnosis , Pilomatrixoma/etiology , Pilomatrixoma/surgery , Cicatrix/pathology , Neoplasm Recurrence, Local , Skin Neoplasms/diagnosis , Skin Neoplasms/etiology , Skin Neoplasms/surgery , Carcinoma/pathology , Hair Diseases/diagnosis , Hair Diseases/etiology , Hair Diseases/surgery
8.
Urban Rail Transit ; 9(1): 31-41, 2023.
Article in English | MEDLINE | ID: mdl-36910688

ABSTRACT

This study aims to analyse the inter-rail modal shift behaviour of suburban rail passengers to examine ridership for the proposed metro extension corridor in Chennai, India. This investigation was conducted in 2019 as part of a feasibility study for the extension of the metro line spanning between Chennai Airport and Kilambakkam, a southern suburb of Chennai. The same origin-destination pair is also served by the suburban rail system. It is an extension of the operating line from Washermenpet to the airport of the Phase I metro project. For this inter-rail competition study, a sample of 272 suburban rail passengers covering work, education and other trip purposes were interviewed using a stated preference questionnaire. Six stated scenarios were considered for analyses which included travel time saving by using the metro along with the fare difference between metro and bus. The study revealed that suburban rail passengers were less concerned about travel time saving and gave priority to fare difference irrespective of trip purpose. This shows the unique metro choice behaviour of suburban rail travellers in the Indian context.

9.
Chemosphere ; 316: 137305, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36410517

ABSTRACT

This research has identified the groundwater potential and vulnerability zones in Tiruchirappalli district of Tamil Nadu, India. The Schlumberger electrode array has been used to conduct vertical electrical sounding (VES) at 95 sites with a maximum electrode spacing of 150 m. The study area comprises of hard rock and sedimentary formations. Geographical Information System (GIS) has been used to integrate the geoelectrical data and to prepare spatial variation maps for various parameters. Finally, groundwater potential and vulnerability zones have been demarcated, and these outputs have been validated using water level and nitrate data, respectively. The Dar-Zarrouk parameters such as longitudinal conductance (S), transverse unit resistance (T), and aquifer anisotropy (λ) have been used along with the spatial variation of resistivity and aquifer thickness to find out groundwater potential areas with the support of GIS. The thickness of topsoil, weathered zone and fractured zone are not uniform in the research area. Top soil plus weathered zone acts as a water table (phreatic) aquifer, which extends up to 38 m from the surface. Fractured zone extends up to 45 m, which acts as a kind of confined/semi-confined aquifer. Open and bore wells have been constructed to tap groundwater from the unconfined (water table) and confined/semi-confined aquifers, respectively. High to very high groundwater potential areas are associated with low resistivity, high thickness, low longitudinal conductance, high transverse unit resistance and high aquifer anisotropy areas. Very high groundwater potential areas are mostly confined to flood plain (alluvium) deposits in the central portion of the study area. High potential areas are noticed in the northern part, whereas low potential areas are noticed in the southern part. The areas with high longitudinal conductance indicate low permeable zones with less possibility of external pollution. Since agriculture is an important activity in the study region, this work will be useful to provide water supply for irrigation as well as for domestic needs.


Subject(s)
Geographic Information Systems , Groundwater , India , Environmental Monitoring , Water Supply
10.
Environ Monit Assess ; 195(1): 223, 2022 Dec 22.
Article in English | MEDLINE | ID: mdl-36544059

ABSTRACT

The present study focuses on the prediction and assessment of the impact of lockdown because of coronavirus pandemic on the air quality during three different phases, viz., normal periods (1 January 2018-23 March 2020), complete lockdown (24 March 2020-31 May 2020), and partial lockdown (1 June 2020-30 September 2020). We identify the most important air pollutants influencing the air quality of Kolkata during three different periods using Random Forest, a tree-based machine learning (ML) algorithm. It is found that the ambient air quality of Kolkata is mainly affected with the aid of particulate matter or PM (PM10 and PM2.5). However, the effect of the lockdown is most prominent on PM2.5 which spreads in the air of Kolkata due to diesel-driven vehicles, domestic and commercial combustion activities, road dust, and open burning. To predict urban PM2.5 and PM10 concentrations 24 h in advance, we use a deep learning (DL) model, namely, stacked-bidirectional long short-term memory (stacked-BDLSTM). The model is trained during the normal periods, and it shows the superiority over some supervised ML models, like support vector machine, K-nearest neighbor classifier, multilayer perceptron, long short-term memory, and statistical time series forecasting model autoregressive integrated moving average. This pre-trained stacked-BDLSTM is applied to predict the concentrations of PM2.5 and PM10 during the pandemic situation of two cases, viz., complete lockdown and partial lockdown using a deep model-based transfer learning (TL) approach (TLS-BDLSTM). Transfer learning aims to utilize the information gained from one problem to improve the predictive performance of a learning model for a different but related problem. Our work helps to demonstrate how TL is useful when there is a scarcity of data during the COVID-19 pandemic regarding the drastic change in concentration of pollutants. The results reveal the best prediction performance of TLS-BDLSTM with a lead time of 24 h as compared to some well-known traditional ML and statistical models and the pre-trained stacked-BDLSTM. The prediction is then validated using the real-time data obtained during the complete lockdown due to COVID second wave (16 May-15 June 2021) with different time steps, e.g., 24 h, 48 h, 72 h, and 96-120 h. TLS-BDLSTM involving transfer learning is seen to outperform the said comparing methods in modeling the long-term temporal dependency of multivariate time series data and boost the forecast efficiency not only in single step, but also in multiple steps. The proposed methodologies are effective, consistent, and can be used by operational organizations to utilize in monitoring and management of air quality.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Humans , COVID-19/epidemiology , Pandemics , Environmental Monitoring/methods , Communicable Disease Control , Air Pollution/analysis , Air Pollutants/analysis , Particulate Matter/analysis
11.
Perspect Clin Res ; 13(4): 194-198, 2022.
Article in English | MEDLINE | ID: mdl-36337372

ABSTRACT

Objectives: The objective was to estimate the proportion of adverse drug reactions (ADRs) to daily regimen antituberculosis treatment (ATT) among the ADRs received in the ADR monitoring center (AMC) of the institution and to describe its pattern. Materials and Methods: This was a descriptive study conducted in the Department of Pharmacology of a Government Medical College in Central Kerala and the period under study was October 2017-June 2020. The data on ADR were entered into a structured pro forma and data were analyzed using SPSS for Windows Version 16.0 (SPSS Inc., Chicago, USA). Results: Of the 643 ADRs, 98 (15.24%) were suspected to be due to the daily regimen of ATT. The most common organ system affected was hepatobiliary 46 (46.9%) namely hepatitis in 35 and asymptomatic elevated liver enzymes in 11 followed by eye with 26 reports of decreased vision. In 96 (97.95%), the suspected ADR had probable causality and in 2 (2.04%) it was possible. Seventy-seven (78.6%) ADR reports were serious as well as moderate-level 4b in severity and 57 (58.16%) were probably preventable. The mean days of onset of ADR after starting the ATT regimen were 56.40 ± 58.29 days (range 1-180). Decrease in vision with a mean duration of 125.23 ± 55.46 days had the longest latency in onset among all the ADRs. Conclusions: Of all the ADRs reported to AMC 15.24% were due to the daily regimen of ATT. Hepatitis was the most common ADR encountered followed by decrease in vision. The majority of the ADRs were probable in causality, serious, moderate-level 4b in severity, and probably preventable.

12.
Chem Commun (Camb) ; 58(84): 11827-11830, 2022 Oct 20.
Article in English | MEDLINE | ID: mdl-36190521

ABSTRACT

Herein, we report a Pd(0)-catalyzed cascade reaction of intramolecular indolyl isocyanide-insertion, isocyanide-initiated scaffold-rearrangement with indolyl migration and redox-neutral process, which affords an efficient access to indolylisoindolinones. Isocyanide as a C(sp3)H-N synthon and the alkyl motif of isocyanide as a hydride source have been explored for the first time.


Subject(s)
Cyanides , Palladium , Molecular Structure , Catalysis , Oxidation-Reduction
13.
Environ Monit Assess ; 194(9): 653, 2022 Aug 06.
Article in English | MEDLINE | ID: mdl-35933570

ABSTRACT

Kolkata has a reputation for being one of the world's most polluted cities, particularly in the post-monsoon months of October, November, and December. Diwali, a Hindu festival, coincides with these months where a large number of firecrackers are set off followed by high emissions of air pollutants. As a result, the air quality index (AQI) deteriorates to "very poor" (301 ≤ AQI ≤ 400) and "poor" (201 ≤ AQI ≤ 300) categories. This situation stays for several days to a month. The present study aims to identify the thresholds for PM2.5 and PM10 that cause the AQI of Kolkata to deteriorate to "very poor" and "poor." For this purpose, we have used a rough set theory-based condition-decision support system to predict the aforementioned categories of AQI. We have developed a Z-number-based novel quantification measure of semantic information of AQI to assess the reliability of the outcomes, as generated from the condition-decision-based decision rules, during post-monsoon season. The result reveals the best possible forecast of AQI with linguistic summarization of the reliability or confidence for different threshold ranges of PM10 and PM2.5. Inverse-decision rules based on rough set theory are utilized to justify and validate the forecasts. The explainability of the condition-decision support system is demonstrated/visualized using a flow graph that maps rough-rule-based different decision paths between input and output with strength, certainty, and coverage. The investigation resulted in an advanced intelligent environmental decision support system (IEDSS) for air-quality prediction.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollution/analysis , Cities , Environmental Monitoring/methods , Particulate Matter/analysis , Reproducibility of Results
14.
J Indian Soc Pedod Prev Dent ; 40(2): 201-207, 2022.
Article in English | MEDLINE | ID: mdl-35859414

ABSTRACT

Background: Irrigation is a crucial aspect of root canal treatment, and it is imperative to employ chelating agents to eliminate the smear layer during biomechanical preparation. They in turn react with mineral content of dentin, leading to decreased strength and increased susceptibility to fracture. Aims: This study aimed to assess and compare mineral loss and microhardness from primary root canal dentin following the usage of different irrigating solutions and determine the least detrimental irrigant among the tested solutions. Materials and Methods: Sixty-six primary anterior teeth were divided into three groups with 22 in each- Group I: 17% ethylenediaminetetraacetic acid (EDTA) Group II: 0.2% Nano chitosan Group III: Pomegranate extract. The decoronated teeth were split longitudinally. Half of it was directly subjected to Vickers test, and the other half was immersed in a magnetic stirrer bath containing test solution to record the mineral loss from solution. Postmicrohardness values were recorded on the specimen and compared with initial values. Statistical Analysis Used: Statistical analysis was done using SPSS software (Version 20, SPSS, IBM, Armonk, NY, U. S. A). Results: Descriptive statistics were calculated, and the groups were compared using analysis of variance test and post hoc Tukey test. Pomegranate extract showed least effect on mineral content and microhardness compared to 17% EDTA and 0.2% nano chitosan. P ≤ 0.05 was considered statistically significant. Conclusion: Pomegranate aril extract showed better results with selected parameters.


Subject(s)
Chitosan , Pomegranate , Chelating Agents/pharmacology , Chitosan/pharmacology , Dentin , Edetic Acid/pharmacology , Humans , Root Canal Irrigants
15.
ChemMedChem ; 17(16): e202200109, 2022 08 17.
Article in English | MEDLINE | ID: mdl-35638162

ABSTRACT

A Core-Linker-Polyamine (CLP) strategy has been exploited to develop new antileishmanial agents. It involves the linker-based assembly of alkyl-polyamine side chain as a potential pharmacophore motif with a privileged heterocyclic motif, 4-arylquinoline. A series of aminoalkyl 4-arylquinoline-2-carboxamides and their analogs were synthesized and tested against L. donovani promastigotes. Among all synthesized derivatives, 10 compounds showed significant antipromastigote activities with more efficacy (IC50 : 4.75-8 µM) than an antileishmanial oral drug Miltefosine (IC50 : 8.9±1.55 µM). Most active aminoalkyl-quinoline-carboxamides 9 a and 9 b, displayed negligible cytotoxicity towards human monocytic (THP-1) macrophages. The compounds show antileishmanial activity by generating mitochondrial superoxide radicals. However, they did not show interference with trypanothione reductase, a redox enzyme of Leishmania. Significant change in the morphology of the L. donovani promastigote by the compounds was observed. The Structure-activity relationship analysis suggest the pharmacophoric importance of alkylpolyamine and carboxamide motifs. In silico evaluation indicated that the investigated active molecules 9 a and 9 b possess important drug-likeness, physicochemical and pharmacokinetic-relevant properties.


Subject(s)
Antiprotozoal Agents , Leishmania donovani , Leishmania , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Humans , Oxidative Stress , Polyamines/pharmacology , Structure-Activity Relationship
16.
Bioorg Med Chem ; 67: 116835, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35617791

ABSTRACT

A strategy of "Nature-to-new" with iterative scaffold-hopping was considered for investigation of privileged ring/functional motif-elaborated analogs of natural aurones. An organocatalyzed umpolung chemistry based method was established for molecular-diversity feasible synthesis of title class of chemotypes i.e. (Z)-2-Arylideneimidazo[1,2-a]pyridinones and (Z)-2-Arylidenebenzo[d]imidazo[2,1-b]thiazol-3-ones. Various biophysical experiments indicated their important biological properties. The analogs showed characteristic anticancer activities with efficiency more than an anticancer drug. The compounds induced apoptosis with arrest in the S phase of the cell cycle regulation. The compounds' significant effect in up/down-regulation of various apoptotic proteins, an apoptosis cascade, and the inhibition of topoisomerases-mediated DNA relaxation process was identified. The analysis of the structure-activity relationship, interference with biological events and the drug-likeness physicochemical properties of the compounds in the acceptable window indicated distinctive medicinal molecule-to-properties of the investigated chemotypes.


Subject(s)
Antineoplastic Agents , Antineoplastic Agents/chemistry , Apoptosis , Cell Line, Tumor , Cell Proliferation , Drug Screening Assays, Antitumor , Imidazoles/chemistry , Imidazoles/pharmacology , Molecular Structure , Structure-Activity Relationship
17.
RSC Med Chem ; 13(3): 320-326, 2022 Mar 23.
Article in English | MEDLINE | ID: mdl-35434631

ABSTRACT

2-Arylquinazolines with a range of alkyl polyamines as side chain/ring functional motifs at the 4th-position were considered for antileishmanial study with the rationale that related heterocyclic scaffolds and polyamine functionalities are present in drugs, clinical trial agents, natural products and anti-parasitic/leishmanial agents. Synthesis involves construction of the 2-arylquinazolin-4-one ring and deoxyamination via deoxychlorination followed by SNAr-based amination or a methodology of SNAr-deoxyamination driven by BOP-mediated hydroxyl-activation. Various alkyl-polyamines important for activities were incorporated. A total of 26 compounds were prepared and screened against Leishmania donovani (Ld) promastigote cells using the MTT assay. Most of the investigated series of compounds showed characteristic leishmanicidal properties. Several compounds showed pronounced leishmanicidal activities (IC50: 5-6.5 µM) with higher efficiency than the antileishmanial drug miltefosine (IC50: 10.5 µM), and relatively less cytotoxicity to macrophage host cells (SI: 9.27-13.5) compared to miltefosine (SI: 3.42). Important pharmacophoric skeletons were identified.

18.
J Egypt Natl Canc Inst ; 34(1): 12, 2022 Mar 21.
Article in English | MEDLINE | ID: mdl-35307789

ABSTRACT

Multimodality is the standard of care in gastric cancer but surgery remains the mainstay of curative treatment. As we are heading towards a more conservative approach for functional preservation without compromising oncological outcomes in all malignancies, the guidelines keeps changing based on various studies.The extent of surgery used to vary between the east and west, with the east performing more radical surgery and the west more reliant on multimodality therapy. This practice has been changing in the recent times.In this article we have reviewed how the treatment protocols of gastric cancer has evolved and modified, highlighting the practice changing trials.


Subject(s)
Stomach Neoplasms , Combined Modality Therapy , Gastrectomy , Humans , Stomach Neoplasms/pathology
19.
J Indian Soc Pedod Prev Dent ; 40(4): 391-397, 2022.
Article in English | MEDLINE | ID: mdl-36861555

ABSTRACT

Background: The complex root canal anatomy of primary root canals is considered to be most challenging. The quality of the root canal preparation plays a significant role in the success of endodontic treatment. Now, there are very few root canal instruments that are capable of cleaning the canal three dimensionally. To evaluate the efficacy of root canal instruments, various technologies have been used; one of the most reliable strategies was cone-beam computed tomography (CBCT). Aim: The aim of this study is to compare the centralization ability and canal transportation of three commercially available pediatric rotary file systems using CBCT analysis. Materials and Methods: Thirty-three extracted human primary teeth with a minimum 7 mm root length were randomly divided into three groups (group I - Kedo-SG Blue, group II - Kedo-S Square, and group III - Pro AF Baby Gold). Biomechanical preparation was done according to the manufacturers instructions. Pre- and postinstrumentation CBCT images were taken for each group to evaluate the remaining dentin thickness thereby assessing the centering ability and the canal transportation ability of different file systems. Results: Significant difference was noticed in canal transportation and centering ability between the three tested groups. Mesiodistal canal transportation was significant at all three levels, whereas buccolingual canal transportation was significant only at the apical third of the root. However, Kedo-SG Blue and Pro AF Baby Gold showed lesser canal transportation compared to Kedo-S Square rotary file system. Mesiodistal centering ability was significant at cervical and apical thirds of the root with Kedo-S Square rotary file system maintaining less canal centricity. Conclusions: All three file systems tested in the study were effective in removing the radicular dentin. However, Kedo-SG Blue and Pro AF Baby Gold rotary file systems showed comparatively less canal transportation and more centering ability than Kedo-S Square rotary file system.


Subject(s)
Cone-Beam Computed Tomography , Dental Pulp Cavity , Infant , Humans , Child , Dental Pulp Cavity/diagnostic imaging , Dental Care , Gold , Root Canal Preparation
20.
Ann Maxillofac Surg ; 12(2): 123-127, 2022.
Article in English | MEDLINE | ID: mdl-36874768

ABSTRACT

Introduction: Local anaesthesia (LA) is the usual drug used in dentistry to reduce intraoperative pain. The efficacy of lignocaine is improved by adding adrenaline as a vasoconstrictor. Adrenaline decreases the systemic absorption of LA and reduces blood loss during the surgical procedure. The study was conducted to observe the effect of adrenaline on blood glucose concentration in patients undergoing tooth extraction. Materials and Methods: The study was conducted on 100 patients needing multiple teeth extraction. On the first appointment, extraction was done using lignocaine without adrenaline (plain), and for the second appointment, extraction was done using lignocaine with adrenaline (1:200,000). Serial blood glucose estimations were carried out at identical intervals on both occasions. Results: Significant difference in blood glucose level was noted when the patients received lignocaine with adrenaline before administration and after 10 min/20 min intervals (P < 0.05). Discussion: Constant vigilance and prudence are recommended while using lignocaine with adrenaline in patients suffering from diabetes mellitus.

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