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Here we present the design of the series of quercetin analogues and their molecular docking study involving the binding of quercetin and its analogues with SARS-CoV2 3CLpro. The scientific literature shows that quercetin compound has been successfully used against SARS-CoV by inhibiting the replication of virus in respiratory epithelial cell through the inhibition of the SARS-CoV main protease (3CLpro.) It was suggested that the modification at position 3 in quercetin structure may produce potent compounds against SARS-CoV2. A series of quercetin analogues were designed and screened for physicochemical and pharmacokinetics parameters. The activities of selected compounds against SARS-CoV2 were screened by molecular modelling and evaluated that analogues, Q5, Q6 and Q13 have the best docking scores (-8.01 to -8.17 kcal/mol) and also better than quercetin, α-ketoamide and current available inhibitors of the same target. The structure-activity relationship (SAR) study revealed that the introduction of the amino group in a designed molecule was highly promising for increasing the inhibitory activity against SARS-CoV2 3CL pro. Moreover, to check the stability and orientation of selected compounds inside the binding pocket, the molecular dynamic simulations were performed for 100 ns. Results revealed that the designed analogues Q1, Q6 and Q13 having lowest binding energies (-8.0, -8.17 and -8.06 kcal/mol respectively) as well as better physicochemical properties, pharmacokinetics, and toxicity profile show their potential to synthesize and develop as the therapeutic agents against corona virus.Communicated by Ramaswamy H. Sarma.

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Seven new hydrazinyl thiazole derivatives of piperidin-4-one (PE3-PE9) have been synthesized by cyclization of intermediate thiosemicarbazone derivative (PE2). Parent molecule (PE1) was synthesized by one pot total synthesis using Mannich condensation reaction. Percent yield of most of the compounds found in between 70-85%. Compounds were identified by spectroscopic analysis. In vivo analgesic activity was examined using tail flick method. One-way ANOVA was used to compare the mean latency time of synthesized derivatives with control and standard. Analgesic activity was discussed in terms of structural differences between compounds. Among allthe derivatives thiosemicarbazone derivative showed good analgesic activity (195.24%). Methoxy (-OCH3) and bromo (-Br) containing thiazole derivative also showed good pain reducing property (167.62%, 203%) at a dose of 30mg/kg.

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The pandemic Coronavirus (Covid-19) is continuously growing and spreading at the highest rate in all over the world. So, it is necessary to produce the new medicinal agents against this virus. The aim of the present study is to design a potent compound against COVID-19. Based on 3C-like main protease and recently developed solved structure (PDB ID: 6Y2F), a series of remdesivir analogs are designed and analyzed by employing molecular modeling against the SARS-CoV-2 by insilico approach. The molecular dynamics (MD) simulation for 500ps was performed to check the stability and orientation to inside the binding pocket for analogs R3, R9, R14 and R15. The study results exhibit that compsound R9 has strong interaction or least binding energy (-10.04kcal/mol) as compare to the other analogues due to the presences of methyl bromide and it may be useful to further investigation in vitro testing against Covid-19.

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Introduction Squamous cell carcinoma of the oral cavity is one of the top 10 malignancies reported globally. Pakistan has a high incidence of oral cancers due to the prevailing poor lifestyle habits/addictions of Pakistanis, and most patients with squamous cell carcinoma present with stage III or IV locally advanced disease. Recommended guidelines indicate surgery as the mainstay of treatment followed by radiotherapy (RT). The addition of induction chemotherapy before surgery or radiation therapy might improve outcomes with increased locoregional control rates. Methods This was a retrospective cohort study comparing the outcomes between surgery followed by concurrent chemoradiotherapy (CCRT) and induction chemotherapy followed by RT. This study primarily aimed to evaluate progression-free survival (PFS) and determine the toxicity of chemotherapy. Results We found out that the mean PFS among patients undergoing surgery and CCRT and those receiving induction chemotherapy followed by RT were 6.40 (± 2.38) months and 7.6 (± 4.76) months, respectively. Conclusion Induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by RT shows satisfactory results with acceptable toxicity. However, the results are not statistically significant but support the already published data on this treatment aspect of oral cavity cancers.

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Experimental design is a significant tool for optimization and validation for the development of HPLC methods to determine API in both human serum and pharmaceutical formulations. In this study, RP-HPLC method is developed and validated for the simultaneous determination of moxifloxacin and NSAIDs. In this experiment, Purospher STAR C18 column with optimum assay conditions (10:90, v/v, water: methanol, pH 2.75) used as mobile phase having flow rate of 1.5mL min-1 and screened at 240 nm. The experimental results exhibit reliability through accuracy (98-102%), precision (0.011-1.85%) and linearity (R2>0.999) in range of 0.15-40µgmL-1. The LOD and LOQ limits for moxifloxacin and NSAIDs are found to be 0.015 and 0.046 µgmL-1 respectively. The significant outcomes conclude that the developed method for assay is effectively suitable to human serum and pharmaceutical formulations and there is no interference from excipients of tablets and serum. The proposed method is useful for drug-interaction and investigation of moxifloxacin with NSAIDs.

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It is known that resistance of bacteria is one of the major issues in drug treatment. To cope this issue, it is required to synthesize new analogues which contest against mutated bacteria. This research study included synthesis of several derivatives of moxifloxacin by adding different phenol and alkyl halide at third position of carboxylic group with esterification reaction and the structures of synthesized derivatives were characterized by spectroscopic techniques i.e. 1H NMR, FT-IR and mass-spectrometry. In continuation, antimicrobial activities of the analogues were also evaluated against number of Gram-positive, Gram-negative bacteria and fungi. The experimental results of novel derivatives exhibit significant antibacterial and antifungal profile in which so many synthesized derivatives influenced a similar and enhanced activity against selected microbes that were S. typhi, P. mirabilis, P. aeruginosa, S. flexneri, B. subtilis as compared to the moxifloxacin. Moreover, few innovative derivatives were also produced better anti-fungal activity against F. solani and T. rubrum. Furthermore, the enzymatic activity of all analogues has been analyzed against urease and carbonic anhydrase and concluded that C2 was selected inhibitor of urease enzyme.

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A series of carboxamide derivatives of moxifloxacin has been synthesized. The synthesized derivatives has been characterization by using spectroscopic techniques such as UV-Vis, IR, H1NMR and Mass spectra, which suggested that incoming group has occupied azabicylo groups of selected moxifloxacin at 7th position. Antimicrobial screening has been systematically carried out against various gram-positive, Gram-negatives and fungi in comparison with parent drug. Enzymatic assay were also performed. The results obtained were statistically analyzed by one way ANOVA. The antimicrobial results reveals that the synthesized derivative of moxifloxacin possess good activities against B. subtilis, F. solani, T. rubrum and P. aeruginosa concluding that derivatives are more potent antimicrobial agents as compared to parent drug. While compound B1 solely possess mild enzymatic activity against urease whereas, no other compounds is active against both urease and carbonic anhydrase.

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