The antioxidative effect of Monodora myristica seed acetone extract and its effect on chemical functional groups were investigated in sickled erythrocytes as well as molecular modeling of the antisickling potentials of its secondary metabolites. The extract was subjected to gas chromatography-mass spectrometry to identify the compounds present, which were then docked into the allosteric-binding site of deoxy-hemoglobin. The extract was incubated with sickled erythrocytes at 37°C for 6, 12, and 24 h and were subjected to antioxidative analysis for reduced glutathione (GSH), superoxide dismutase (SOD), catalase, and lipid peroxidation (LPO). Chemical functional group of the treated cells was analyzed via Fourier transform infrared spectroscopy (FTIR). The predominant compounds identified were 17-octadecynoic acid; oleic acid, androstan-3-one, 17-hydroxy-2-methyl- (2.beta.,5.beta.,17.beta.)-; estran-3-one, 17-(acetyloxy)-2-methyl-, (2.alpha., 5.alpha., 17.beta.), and (+)-3-carene, 10-(acetylmethyl)-. They all fitted well within the active site of Hb with good binding affinity, as evidenced by the negative CDocker interaction energies of their complexes ranging between -54.4 and -26.7 kcal/mol. Treatment with the extract exacerbated SOD and catalase activities as well as GSH level, while LPO was suppressed. This antioxidative activity was time and/or dose dependent, with 6 and 12 h incubation showing the optimum activity. FTIR analysis of the treated cells showed the presence of hydrophobic functional groups. The synergetic molecular interaction of the major compounds of the extract with the α-dimer of Hb depicts an antisickling effect of M. myristica acetone extract. This is accompanied by exacerbation of endogenous antioxidant enzymes activity and modification of the functional chemistry of the cells.

IntroductionVaccination is an effective strategy for preventing SARS-CoV-2 infection and associated mortality. Renal Transplant Recipients (RTRs) are vulnerable to acquiring infection and high mortality due to their immunocompromised state. Varying responses to the different vaccines, depending on types of vaccines and population, have been reported. Vaccines supply is also limited. The current study evaluated the seroconversion rate after SARS-CoV-2 infection and 2 doses of either COVAXIN™ or COVISHIELD™ vaccination in RTR.MethodsThe serum anti-SARS-CoV-2 spike protein neutralizing antibody titer was measured in 370 RTRs who acquired SARS-CoV-2 infection (n=172), yet not vaccinated; and those vaccinated with COVAXIN™ (n=78), and COVISHIELD™ (n=120) by chemiluminescence microparticle immunoassay methods from serum.ResultOverall, the seroconversion rate either after vaccination or infection was 85.13% (315/370). The vaccine-associated seroconversion was 80.30% (159/198). SARS-CoV-2 infection-associated seroconversion was 90.69% (156/172), COVISHIELD™ associated seroconversion was 79.2% (95/120), and COVAXIN™ associated seroconversion was 82.05% (64/78). The median IgG titer in the SARS-CoV-2 infection group was 646.50 AU/ml (IQR: 232.52-1717.42), in the COVAXIN™ group was 1449.75 AU/ml (IQR: 400.0-3068.55), and the COVISHIELD™ vaccination group was 1500.51 AU/ml (IQR: 379.47-4938.50). The seroconversion rate and antibody titers were similar irrespective of the place of sampling. Patient’s age-associated seroconversion in <45 years was 88.01% (213/242), 45.1-60 years was 83.18% (94/113), and > 60 years was 58.3% (7/12).ConclusionsBoth infection and vaccination induce robust antibody formation in RTRs. The seroconversion rate after SARS-CoV-2 infection was higher but with a lower antibody titer than vaccines. The vaccines, COVAXIN™ and COVISHIELD™, induce more elevated antibody titers than natural infection. The seroconversion rate and antibody titer in Indian RTRs appears to be better than in the western population, irrespective of their vaccination status.

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A series of quinazolin‐4‐one Schiff bases were synthesized and tested in vitro for their cytotoxicity against two cancerous cell lines (MCF‐7, Caco‐2) and a human embryonic cell line (HEK‐293) including their antibacterial evaluation against two Gram‐positive and four Gram‐negative bacterial strains. Most of the quinazoline‐Schiff bases exhibited potent cytotoxicity against Caco‐2. 3‐[(Z)‐({4‐[(But‐2‐yn‐1‐yl)oxy]phenyl}methylidene)amino]‐2‐methylquinazolin‐4(3H)‐one (6f) with the O‐butyne functional group displayed three‐fold higher cytotoxic activity (IC50=376.8 μM) as compared to 5‐fluorouracil (5‐FU; IC50=1086.1 μM). However, all compounds were found to be toxic to HEK‐293, except for 3‐[(Z)‐({4‐[(2,4‐difluorophenyl)methoxy]phenyl}methylidene)amino]‐2‐methylquinazolin‐4(3H)‐one (6h) that showed ∼three‐fold lower toxicity and higher selectivity index than 5‐FU. Structure–activity relationship (SAR) analysis revealed that O‐alkylation generally increased the anticancer activity and selectivity of quinazoline‐4‐one Schiff bases toward Caco‐2 cells. The fluorinated Schiff‐base generally exhibited even more significant cytotoxic activity compared to their chlorine analogs. Surprisingly, none of the quinazoline‐4‐one Schiff bases displayed encouraging antibacterial activity against the bacterial strains investigated. Most of the compounds were predicted to show compliance with the Lipinski parameters and ADMET profiles, indicating their drug‐like properties.

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