Decoding the binding interaction of steroidal pyridines with bovine serum albumin using spectroscopic and molecular docking techniques.

The present study reports a comprehensive and conformational aspect of binding of steroidal pyridines (1-6) with a model transport protein, bovine serum albumin (BSA) by fluorescence, UV-visible, circular dichroism, and molecular docking techniques. Quenching of BSA emission was attributed to the formation of the ground state complex after the compound (1-6) binds to the backbone of the protein. Synchronous fluorescence spectra reveals changes in the microenvironment of the aromatic residues. UV-visible absorption spectra further reiterate the quenching mechanism to be static and binding of compound (1-6) results in the formation of a ground-state complex. Circular dichroism spectra indicated that compound 1-3 causes unfolding and compound 4-6 leads to the stabilization of the protein structure. In addition, a molecular docking study revealed the binding pocket for the formation of the ligand-protein complex through hydrogen bonding and hydrophobic interactions. Furthermore, hemolytic activity suggested that the compounds (1-6) are biocompatible in nature. Evaluation of such steroid-protein interaction helps in better understanding of the biomolecular interaction of steroidal compounds with biomacromolecule and opens up new approaches in steroid based drug-design process.

Retrospective analysis of the role of retrobulbar amphotericin-B injection in the management of COVID-19 associated rhino-orbito-cerebral-mucormycosis.

Introduction: Rhino-orbito-cerebral-mucormycosis (ROCM) is the most common form of mucormycosis observed during the second wave of COVID-19 where a steep rise in the number of cases was seen. The orbital form is almost always associated with fungal sinusitis. Among the various treatment modalities available, the role of retrobulbar Amphotericin-B injections is under-reported. This study is conducted to determine the role of transcutaneous retrobulbar amphotericin-B (TRAMB) in the management of COVID-19 associated ROCM. Methods: a retrospective analysis of 61 patients of COVID-19 associated ROCM was done, who met the inclusion criteria and presented to a tertiary care center, between May to August 2021. These patients were administered TRAMB (deoxycholate/emulsion form) along-with systemic amphotericin B. All the patients were evaluated for clinical improvement. Results: out of 61 patients, 58 (95.08%) showed overall improvement. 40 patients (65.57%) stabilized or improved clinically and 3 patients succumbed to the illness due to advanced systemic mucormycosis and acute kidney failure. Sixteen out of 58 patients underwent orbital exenteration. Out of remaining 43 patients, 35 showed complete recovery of orbital and ocular disease and the disease stabilized in eight patients. Seven patients demonstrated TRAMB associated ocular complications which however completely resolved in six patients. Conclusion: to the best of the author´s knowledge, regression of orbital mucormycosis with improvement in ptosis, proptosis, ocular motility and stabilization of visual acuity are scarcely reported in literature. Further TRAMB as a globe non-deforming treatment modality is an option available for ROCM.

Synthesis of steroidal dihydropyrazole derivatives using green ZnO NPs and evaluation of their anticancer and antioxidant activity.

Zinc oxide nanoparticles (ZnO NPs) were synthesized by a green method using Azadirachta indica leaf extract. The structure of the prepared ZnO (NPs) were characterized by FT-IR, XRD, SEM-EDX and TEM analyses. The biosynthesized ZnO (NPs) were then used as a catalyst for the synthesis of steroidal dihydropyrazole derivatives through a one-pot multicomponent reaction involving phenyl acetylene and hydrazine derivatives. The anticancer activity of newly synthesized compounds were evaluated against three cancer cell lines namely HeLa (human cervical carcinoma), Hep3B (human hepatocellular carcinoma) and MCF7 (human breast adenocarcinoma) by MTT assay. The tested compounds were found to be active against all cancer cell lines and less toxic towards normal peripheral blood mononuclear cells (PBMCs). Antioxidant activity have also been investigated via free radical scavenging ability using DPPH, FRAP and ABTS assay. The tested compounds were found to exhibit moderate to good antioxidant activity which increases with increase in the concentration of steroidal dihydropyrazoles. Among all the tested steroidal dihydropyrazoles, compound 17 is found to be most active.

Multi-Component One-Pot Assisted Synthesis, Anti-bacterial Capabilities, and Scanning Electron Microscopy of Novel Corticosteroid Thiopyran.

BACKGROUND: Corticosteroids are an important group of polycyclic compounds having a wide range of pharmacological and physiological properties. Thiopyran derivatives are important building blocks of many biologically active compounds. OBJECTIVE: Keeping in mind the wide range of applications of corticosteroids and thiopyran, herein we intend to develop a simple and efficient strategy to synthesize steroidal thiopyran derivatives starting with different commercially available corticosteroids and study their biological properties. MATERIALS AND METHODS: To achieve our aim, we employed a one-pot multi-component synthesis of steroidal thiopyran derivatives by the reaction of corticosteroids, malononitrile, and carbon disulphide in the presence of triethylamine as a catalyst. RESULTS AND DISCUSSION: An array of novel thiopyran compounds was obtained with the highest product yield using Et3N. Scanning electron microscopy analysis manifested agglomeration pertaining to brick-shaped crystals of corticosteroid thiopyran. Synthesized compounds were also found to be active as anti-bacterial agents. CONCLUSION: We describe a facile one-pot multi-component synthesis of corticosteroid thiopyran derivatives, which are found to possess anti-bacterial activity. Excellent yields of the products, simple work-up, easily available starting materials, and non-chromatographic purification are some of the main advantages of this protocol.

Steroidal thiazolidinone derivatives: Design, synthesis and their molecular interaction with human serum albumin.

A series of steroidal thiazolidinone derivatives have been synthesized through one-pot multicomponent reaction involving steroidal ketone, thiosemicarbazide/methyl-thiosemicarbazide and DMAD in presence of AlCl3 as a Lewis acid catalyst. Among all the synthesized steroidal thiazolidinone derivatives, compound 7-9 (ST 7-9) were investigated for their in vitro molecular interaction with human serum albumin. Intrinsic fluorescence spectroscopy, constant wavelength synchronous fluorescence spectroscopy, circular dichroism and UV-visible absorption techniques have been exploited to characterize the binding phenomena in phosphate buffer solution at pH 7.4. The experimental results indicated that ST 7-9 bind to HSA and the intrinsic fluorescence of HSA was quenched through static quenching mechanism. The binding parameters were calculated and the binding constants obtained were 1.44 × 105 M-1 for ST 7, 0.84 × 105 M-1 for ST 8 and 1.06 × 105 M-1 for ST 9. Circular dichroism analysis confirms that the presence of ST 7-9, altered the secondary structure of HSA due to partial unfolding of the polypeptide chain. Furthermore, hemolytic activity assay demonstrated that the synthesized steroidal thiazolidinone derivatives have good compatibility towards human red blood cells. Finally, molecular docking studies revealed that the steroidal thiazolidinones can bind in the hydrophobic cavity of HSA, by hydrophobic and hydrogen bonding interaction. These results provided valuable information about the binding mechanism of ST 7-9 with HSA and play a pivotal role in the development of steroidal heterocycle inspired compounds.

Facile one-pot multicomponent synthesis and molecular docking studies of steroidal oxazole/thiazole derivatives with effective antimicrobial, antibiofilm and hemolytic properties.

A series of steroidal oxazole and thiazole derivatives have been synthesized employing thiosemicarbazide/semicarbazide hydrochloride and ethyl 2-chloroacetoacetate with a simple and facile one-pot multicomponent reaction pathway. The antimicrobial activity of newly synthesized compounds were evaluated against four bacterial strains namely Gram-negative (Escherichia coliand Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) in addition to pathogenic fungi (Candida albicans and Cryptococcus neoformans). Bioactivity assay manifested that most of the compounds exhibited good antimicrobial activity. To provide additional insight into antimicrobial activity, the compounds were also tested for their antibiofilm activity against S. aureus biofilm. Moreover, molecular docking study shows binding of compounds with amino acid residues of DNA gyrase and glucosamine-6-phosphate synthase (promising antimicrobial target) through hydrogen bonding interactions. Hemolytic activity have been also investigated to ascertain the effect of compounds over RBC lysis and results indicate good prospects for biocompatibility. The expedient synthesis of steroidal heterocycles, effective antibacterial and antifungal behavior against various clinically relevant human pathogens, promising biocompatibility offer opportunities for further modification and potential applications as therapeutic agents.