Exploring antibiofilm potential of some new imidazole analogs against C. albicans: synthesis, antifungal activity, molecular docking and molecular dynamics studies.

A series of 1, 2, 4, 5-tetrasubstituted imidazole derivatives were synthesized and their antibiofilm potential against Candida albicans was evaluated in vitro. Two of the synthesized derivatives 5e (IC50 = 25 µg/mL) and 5m (IC50 = 6 µg/mL),displayed better antifungal and antibiofilm potential than the standard drug Fluconazole (IC50 = 40 µg/mL) against C. albicans. Based on the in vitro results, we escalated the real time polymerase chain reaction (RT-PCR) analysis to gain knowledge of the enzymes expressed in the generation and maintenance of biofilms and the mechanism of biofilm inhibition by the synthesized analogues. We then investigated the possible interactions of the synthesized compounds in inhibiting agglutinin-like proteins, namely Als3, Als4 and Als6 were prominently down-regulated using in-silico molecular docking analysis against the previously available crystal structure of Als3 and constructed structure of Als4 and Als6 using the SWISS-MODEL server. The stability and energy of the agglutinin-like proteins-ligand complexes were evaluated using molecular dynamics simulations (MDS). According to the 100 ns MDS, all the compounds remained stable, formed a maximum of 3, and on average 2 hydrogen bonds, and Gibb's free energy landscape analysis suggested greater affinity of the compounds 5e and 5m toward Als4 protein.Communicated by Ramaswamy H. Sarma.

Review on advancements of pyranopyrazole: synthetic routes and their medicinal applications.

Pyranopyrazoles are among the most distinguished, biologically potent, and exciting scaffolds in medicinal chemistry and drug discovery. Synthesis and design of pyranopyrazoles using functional modifications via multicomponent reactions (MCRs) are thoroughly found in synthetic protocols by forming new C-C, C-N, and C-O bonds. This review aims to focus on the biological importance of pyranopyrazoles as well as on a diverse synthetic approach for their synthesis using various catalytic systems such as acid-catalyzed, base-catalyzed, ionic liquids and green media-catalyzed, nano-particle-catalyzed, metal oxide-supported catalysts, and silica-supported catalysts. In this review, we have summarized data on the advancements in synthesizing pyranopyrazole from the last two decades to the mid-2023 and research papers describing the importance of these scaffolds. This review will be significant for synthetic organic chemists and researchers working in organic chemistry.

Unraveling the access to the regioselective synthesis of highly functionalized pyranopyrazoles using an ionic liquid catalyst.

An efficient and green strategy for the regioselective synthesis of highly functionalized pyranopyrazole via one-pot condensation of 3-methyl-1-phenyl-5-pyrazolone or EAA and hydrazine hydrate, substituted aromatic aldehydes with NMSM [(E)-N-Methyl-1-(methylthio)-2-nitro-ethenamine] in the existence of IL [(EMIM)Ac] as catalyst with solvent-free condition (SFC) is described. This domino protocol produces biologically substantial heterocycles through Knoevenagel condensation proceeded by Michael addition and O-cyclization with an eradication of methanethiol group, which create the one stereo-center and creation of "C-C, C-N, C-O, C=C, C=N, bonds." The final product is produced by exceptionally easy filtering after the reaction mass was triturated with ethanol. The strategy's noteworthy features include the use of biodegradable IL catalyst, excellent to exceptional yield with rapid reaction times, applicability to a wide range of substrate, clear reaction profile, and straightforward workup process.

Aggregation induced emission (AIE) materials for mitochondria imaging.

Mitochondria are energy producing organelle of the eukaryotic cells. The main activities of mitochondria monitored by various marker molecules are autophagy detection, estimation of Reactive Oxygen Species (ROS), mitochondrial death and Photodynamic therapy in cancer cells. Due to the advantages of specificity and sensitivity, aggregation induced emission (AIE) is now popular for the mitochondria labeling. In this chapter, we would like to discuss three major types of AIEgens probe used in mitochondrial staining. There are three different types of AIEgens available for mitochondrial detection and sensing based on their different structural motifs. The first type of AIEgens is tetraphenylethene (TPE) based molecules. Due to simple engineering architecture, TPE based AIEgens are widely employed in bioimaging applications. AIEgen such as triphenylphosphine (TPP), and triphenylamine (TPA) are also employed as a novel building block. These are successfully used as exceptional lipid droplet (LD)-specific bio probes in cell imaging, assurance of cell combination, and photodynamic cancer cell removal. The third group is the miscellaneous AIEgens probe involved in mitochondria imaging.

Androgen Insensitivity Syndrome: A rare genetic disorder.

BACKGROUND: Androgen Insensitivity Syndrome (AIS) is a rare X-linked recessive androgen receptor (AR) disorder with 46XY karyotype. Partial AIS affects 5-7 per 1,000,000 genetically male individuals whereas Complete AIS affects 2-5 per 100,000 genetically male individuals. CAIS CAIS is characterized by complete resistance to the action of androgens. PRESENTATION OF CASE: 17-year patient presented with swelling in bilateral inguinal region. Patient also complained of primary amenorrhea with serum FSH and LH levels being raised, serum testosterone level much above normal range. MRI Pelvis revealed agenesis of vagina, uterine body, both ovaries and cervix. Bilateral testes were noted in bilateral superficial inguinal ring. Bilateral orchidectomy was done and the patient was advised estrogen substitution therapy. DISCUSSION: CAIS is usually diagnosed at puberty, when the patient presents with primary amenorrhea. Karyotype has to be mapped in order to differentiate from other genetic disorders. Orchidectomy should be done to avoid risk of malignancy of undescended intra-abdominal testes (3.6 % at 25 years old, and 33 % at 50 years old, reported by various studies). Hormonal substitution therapy should be administered. Comprehensive psychiatric assessment and intervention go a long way in alleviating distress and enhancing quality of life. CONCLUSION: Androgen Insensitivity Syndrome requires expert and sympathetic handling. Close collaboration between surgeon, gynaecologist and psychologist is essential for proper management of complete androgen insensitivity syndrome.

Synchronous mixed germ cell tumor of testis and renal cell carcinoma: A rare presentation.

INTRODUCTION: Synchronous presentation of mixed germ cell tumor of testis and renal cell carcinoma is a rare presentation and has not been reported in literature. RCC accounts for 3% of all adult malignant neoplasms (Marzouk et al., 2014). It is the most lethal urologic cancers. Testicular cancer is of generally aggressive form and is the most common form of cancer in young men aged 15-35 years. PRESENTATION OF CASE: We report a case of incidental finding of left renal cell carcinoma with mixed germ cell tumor of right testis in our patient. A 36 years old male patient came with complaints of painless swelling in the right side of the scrotum since 1 year. On palpation a hard swelling of size 5 x 4 cm was palpable in right scrotum. Ultrasonography suggested likelihood of a neoplastic etiology. On Contrast enhanced CT of abdomen, a well defined mass in the lower pole of left kidney likely to be an Oncocytoma, which was not palpable. CT guided biopsy of renal mass, was suggestive of epithelial renal tumor probably oncocytoma or low grade renal cell carcinoma. DISCUSSION: In literature there are very few cases reported of metachronous mixed germ cell tumor of testis and renal cell carcinoma. There are 12 reports of patients having metachronous testicular and renal malignancy. During the metastatic work up to mixed germ cell tumor we found the mass in the left kidney which was ultimately diagnosed to be renal cell carcinoma. The management of both the malignancies depend on their merit and is a real challenge for a surgeon. CONCLUSION: Treatment strategies for both malignancies depend on accurate clinical staging and should be integrated to provide optimal results.

Ionic liquid promoted synthesis, antibacterial and in vitro antiproliferative activity of novel α-aminophosphonate derivatives.

Ionic liquid ethyl ammonium nitrate is used as an excellent catalyst and solvent for three-component one-pot reaction of an aldehydes, amines and diethylphosphite to form novel α-aminophosphonates at room temperature. Among the various catalysts, the preparation of ethyl ammonium nitrate is an environmental friendly, cost effective and recyclable catalyst. Compounds 4b, 4c, 4d, 4f and 4j were found more potent antibacterials against pathogenic microorganisms. Whereas, compounds 4a, 4g, 4h and 4j inhibits growth of active Escherichia coli NCIM 2645 and Salmonella typhi NCIM 2501. Compound 4j was found a promising antiproliferative agent against A549 and SK-MEL2 human melanoma cell lines.