Recent developments in the synthesis of hybrid antimalarial drug discovery.

In this 21st century, Malaria remains a global burden and causes massive economic trouble to disease-endemic nations. The control and eradication of malaria is a major challenge that requires an urgent need to develop novel antimalarial drugs. To overcome the aforementioned situation, several researchers have given significant effort to develop hybrid antimalarial agents in the search for new antimalarial drugs. Hence, we have summarized those developments of hybrid antimalarial agents from 2017 to till date. This review illustrates the current progress in the recent synthesis of hybrid antimalarial agents along with focusing on their antimalarial evaluation to find the most potent hybrids. This present mini-review will also be useful for the scientific community for the development of new antimalarial drugs to eradicate malaria.

Recent advances on synthesis of C-glycosides.

In recent years, C-glycosides have emerged as significant building blocks for many naturally occurring alkaloids and pharmaceutically active drug molecules. Therefore, significant efforts have been devoted to the construction of structurally important C-glycosidic linkages in carbohydrate compounds. Herein, we have summarized the recent developments of diverse synthesis of C-glycoside core between the time period from 2019 to 2022 focusing on different catalytic strategies, such as (i) transition-metal, and (ii) metal-free catalytic approaches. Further, the transition metal catalyzed C-glycosylations have been categorized into four sub classes: (a) metal based C-H activation, (b) cross-coupling reaction, (c) glycosyl radical intermediate-based process, and (d) Others.

Base mediated green synthesis of enantiopure 2-C-spiro-glycosyl-3-nitrochromenes.

A novel green synthetic methodology has been developed to obtain enantiopure (2S)-2-C-spiro-glycosyl-3-nitrochromenes following the oxa-Michael-aldol condensation reaction of sugar derived 3-C-vinyl nitro olefins with substituted salicylaldehydes using Et3N as a base under neat conditions at rt-40 °C. The stereochemistry of the product is confirmed by a single crystal X-ray study. Several advantages are associated with this protocol such as cost effectiveness, easy accessibility, short reaction time, high yields, wide substrate scope and high enantiopurity.

Diastereoselective synthesis of novel spiro indanone fused pyrano[3,2-c]chromene derivatives following hetero-Diels-Alder reaction and in vitro anticancer studies.

The development of concise methods for the synthesis of small functionalised spirocyclic molecules is important in the search of new bioactive molecules. To contribute this, here we represent a diastereoselective oxa-hetero-Diels-Alder reaction for the synthesis of novel spiro indanone fused pyrano[3,2-c]chromene derivatives and studied their in vitro anticancer activities. Using previously less explored cyclic ketone i.e. indane-1,3-dione and 3-vinyl-2H-chromene derivatives, we obtained novel spiro-heterocyclic frameworks at the interphase between "drug-like" molecules and natural products. Various spiro indanone fused pyrano[3,2-c]chromene derivatives were synthesized regiospecifically bearing a quaternary stereocenter in high yields (up to 85%) with excellent diastereoselectivity in toluene using 4 Å MS as additive under reflux condition at 120 °C. In vitro cytotoxic studies of these compounds against MCF-7 (breast cancer), HCT-116 (colon cancer), H-357 (oral cancer), MD-MB-231(Breast cancer) cell lines were evaluated by MTT {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide} assay in vitro. The screening results revealed that many of the compounds are showing moderate to high levels of anticancer activities against the tested cancer cell lines and some displayed potent inhibitory activities in comparison to the commercial anticancer drug 5-fluorouracil (5-FU). Among the series, compound 3'c showed most potent cytotoxicity (15.0-27.5 µM) in three cancer cell lines (MCF-7, HCT-116 and MD-MB-231).

Treatment Experiences of Women with Reproductive Cancers in Odisha, India: A Qualitative Exploration of Enablers and Barriers

Introduction: Cancer continues to be a major menace to our Indian society notwithstanding significant progress in diagnosis and treatment. In India cancer mortality rates in women are high compared to other countries, despite efforts to improve survival through the development of effective detection techniques and increased numbers of viable treatment options. Indian women's advanced stage of disease at diagnosis is largely attributable to delay in seeking treatment. The present qualitative inquiry was conducted with the aim of capturing the treatment experiences of patients with gynecology cancer at a tertiary care hospital and understanding the barriers, enablers, stress and apprehension they experience during the treatment phases. Methods: Twenty-one in-depth interviews were conducted with women diagnosed with gynecological cancers and undergoing at least one treatment intervention in the Inpatient Department (IPD). Theme guides were developed with a review of the literature and consultation with experts in the field. Data were collected by trained investigators who were well versed with the local language and analyzed using an inductive approach. Results are presented in the form of core- and sub-themes evolved during this process. Results: Out of the 21 respondents, 19 were married and 2 were widows. Nineteen had attained more than secondary qualifications. Nearly all women described themselves as 'housewives'. Amongst participants, 13 were diagnosed with breast cancer, 5 with ovarian cancer and 3 with cervical cancer. Thematic framework analysis of the transcripts yielded six key themes: 1) best and worst experiences during the treatment process; 2) financial and emotional stress; 3) care giving and social support; 4) satisfaction with the medical staff; 5) preferences for a female gynecologist and female gynecology ward; and 6) prompt and free treatment. Quotable quotes were presented in the table against every theme. Conclusion: Strengths in the Indian health care delivery system need to be built upon, while attention should be paid to developing effective psychosocial interventions, with a robust financial protection plan for patients and their involvement in decision making. Counselling of patients should be made part of a routine protocol.

Design and characterization of cefuroxime axetil biphasic floating minitablets.

Biphasic floating minitablets of cefuroxime axetil were prepared by melt granulation technique using two different grades of gelucire namely 50/13 and 43/01 to maintain constant plasma drug concentration. Loading dose of cefuroxime axetil was formulated as immediate release (IR) minitablets by using hydrophilic grade of gelucire 50/13. Maintenance dose was formulated as floating sustained release (SR) minitablets by using hydrophobic grade of gelucire 43/01. The prepared IR and SR granules were subjected to micromeritic studies and scanning electron microscopy. Fourier transform infrared spectroscopy (FT-IR) study revealed that drug and selected carriers were compatible. In vitro dissolution study of optimized IR minitablets showed more than 85% of loading dose dissolved within 30 min. Optimized SR minitablets showed zero lag time with floating duration more than 12 h. The drug release from SR minitablets was linear with square root of time with non-Fickian diffusion-controlled release. The optimized batch of minitablets was filled into 0 size hard gelatin capsule. In vitro dissolution study for capsule showed an immediate burst release followed by SR up to 12 h. There is no significant change in dissolution data after storage at 40 °C and 75% RH for three months. Microbiological assay of dissolution samples of optimized minitablets filled in capsules showed proportionate increase in inhibition of growth against Escherichia coli up to 12 h samples. In vivo bioavailability study in albino rabbits showed three times improvement in oral bioavailability.

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines.

Enantioselective organocatalysis has become a field of central importance within asymmetric chemical synthesis and appears to be efficient approach toward the construction of complex chiral molecules from simple achiral materials in one-pot transformations under mild conditions with high stereocontrol. This review addresses the most significant synthetic methods reported on chiral-amine-catalyzed tandem Michael conjugate addition of heteroatom-centered nucleophiles to α,ß-unsaturated compounds followed by cyclization reactions for the enantioselective construction of functionalized chiral chromenes, thiochromenes and 1,2-dihydroquinolines in optically enriched forms found in a myriad of bioactive natural products and synthetic compounds.

Design and Synthesis of 3,5-Disubstituted 1,2,4-Oxadiazole Containing Retinoids from a Retinoic Acid Receptor Agonist.

We previously synthesized novel retinoid libraries, and after screening for bioactivity found one compound BT10 that functions as a specific agonist for retinoic acid receptors. This lead compound was further derivatized using SAR and LRD to obtain 3,5-disubstituted-1,2,4-oxadiazole-containing retinoids. The new oxadiazole (amide bioisosters)-containing retinoids (compounds 1, 2, 3, 4, 5, and 6) were synthesized in 42-65% yield by reacting with (E)-4-((3-ethyl,2-4,4,4-trimethylcyclohex-2-enylidene)methyl)benzoic acid and phenyl substituted amidoxime in DMF using CDI as the coupling reagent. The biological activities of the synthesized compounds are currently being evaluated.

Synthesis of function-oriented 2-phenyl-2H-chromene derivatives using L-pipecolinic acid and substituted guanidine organocatalysts.

Organocatalytic domino oxa-Michael/aldol reactions between salicylaldehyde with electron deficient olefins are presented. We screened guanidine, 1,1,3,3-tetramethylguanidine (TMG) and L-pipecolinic acid as organocatalysts for this transformation. 3-Substituted 2-phenyl-2H-chromene derivatives are synthesized with high yields and with poor enantioselectivity (5-17% ee) using L-pipecolinic acid while TMG works well with cinnamaldehyde without using co-catalyst. These 3-substituted-2-phenyl-2H-chromene derivatives are further derivatized to synthesize triazole and biotin-containing chromene derivatives, to facilitate purification of protein targets.