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Healthcare systems worldwide are struggling to find ways to fund the cost of innovative treatments such as gene therapies, regenerative medicine, and monoclonal antibodies (mAbs). As the world's best known mAbs are close to facing patent expirations, the biosimilars market is poised to grow with the hope of bringing prices down for cancer treatment and autoimmune disorders, however, this has yet to be realized. The development costs of biosimilars are significantly higher than their generic equivalents due to therapeutic equivalence trials and higher manufacturing costs. It is imperative that academics and relevant companies understand the costs and stages associated with biologics processing. This article brings these costs to the forefront with a focus on biosimilars being developed for Rheumatoid Arthritis (RA). mAbs have remarkably changed the treatment landscape, establishing their superior efficacy over traditional small chemicals. Five blockbuster TNFα mAbs, considered as first line biologics against RA, are either at the end of their patent life or have already expired and manufacturers are seeking to capture a significant portion of that market. Although in principle, market-share should be available, withstanding that the challenges regarding the compliance and regulations are being resolved, particularly with regards to variation in the glycosylation patterns and challenges associated with manufacturing. Glycan variants can significantly affect the quality attributes requiring characterization throughout production. Successful penetration of biologics can drive down prices and this will be a welcome change for patients and the healthcare providers. Herein we review the biologic TNFα inhibitors, which are on the market, in development, and the challenges being faced by biosimilar manufacturers. [ABSTRACT FROM AUTHOR]

In this work, non-fullerene based derivatives (DTCD2-DTCD8) with D1-π-D2-π-A architecture were tailored by alteration of terminal acceptor group of a reference molecule (DTCR1) in order to investigate their non-linear optical (NLO) behavior. The effect of peripheral acceptor and donor sites on designed configuration for optical communication and electronic response was examined using DFT based calculations. The natural bond orbitals (NBOs), frontier molecular orbitals (FMOs), UV–Vis analysis, nonlinear optics (NLO), density of states (DOS) and transition density matrix (TDM) were calculated at M06-2X/6-311G(d,p) level. The energy gap of DTCD2-DTCD8 was found to be lowered (Δ E = 3.970–3.603 eV) with wider absorption spectra as compared to that of DTCR1 (4.221 eV). All the derivatives (DTCD2-DTCD8) demonstrated significant NLO behavior than the reference (DTCR1). Among all the designed compounds, DTCD8 exhibited the highest dipole moment (µ total = 4.777 D) , average linear polarizability [〈 α 〉 = 1.920 × 10−22 esu ], first hyperpolarizability (β total = 10.58 × 10−28 esu) and second hyperpolarizability (γ total = 8.028 × 10−33 esu) as it showed the lowest energy gap (3.603 eV) as compared to the other molecules. [ABSTRACT FROM AUTHOR]

A novel series of thiophene derived Schiff bases and their transition metal- [Co(II), Cu(II), Zn(II), Ni(II)] based compounds are reported. The Schiff bases act as tridentate ligands toward metal ions via azomethine-N, deprotonated-N of ammine substituents and S-atom of thienyl moiety. The synthesized ligands along with their metal complexes were screened for theirin vitroantibacterial activity against six bacterial pathogens(Escherichia coli,Shigella flexneri,Pseudomonas aeruginosa,Salmonella typhi,Staphylococcus aureusandBacillus subtilis) and for antifungal activity against six fungal pathogens (Trichophytonlongifusus,Candida albicans,Aspergillus flavus,Microsporum canis,Fusarium solaniandCandida glabrata). The results of antimicrobial studies revealed the free ligands to possess potential activity which significantly increased upon chelation. [ABSTRACT FROM AUTHOR]

A new series of compounds derived from thiophene-2-carboxamide were synthesized and characterized by IR,1H-NMR and13C-NMR, mass spectrometry and elemental analysis. These compounds were further used to prepare their Co(II), Ni(II), Cu(II) and Zn(II) metal complexes. All metal(II) complexes were air and moisture stable. Physical, spectral and analytical data have shown the Ni(II) and Cu(II) complexes to exhibit distorted square-planar and Co(II) and Zn(II) complexes tetrahedral geometries. The ligand (L1) and its Cu(II) complex were characterized by the single-crystal X-ray diffraction method. All the ligands and their metal(II) complexes were screened for theirin-vitroantimicrobial activity. The antibacterial and antifungal bioactivity data showed that the metal(II) complexes were found to be more potent than the parent ligands against one or more bacterial and fungal strains. [ABSTRACT FROM AUTHOR]

Fullerene-free organic chromophores have drawn considerable attention as successful photonic devices for organic solar cells. So, a series of novel non-fullerene-based donor molecules (HBTD2–HBTD9) were fabricated via structural modification of the terminal acceptor groups from HBTR1. In order to achieve the photovoltaic, photophysical, and electronic behavior of fore-said compounds, density functional theory/time-dependent density functional theory (DFT/TD-DFT) based analyses were accomplished at B3LYP functional along with 6-311G(d,p) basis set. The optical and electrical characteristics of the derivatives were compared with HBTR1 architecture. All designed molecules exhibited a lower E HOMO - E LUMO band gap (2.183–4.106 eV) with a red shift in absorbance compared to the reference compound (4.179 eV). All derivatives (HBTD2–HBTD9), except HBTD3 , showed a greater exciton dissociation rate due to low binding energy (E b = −0.337 to 1.400 eV) when compared with HBTR1 (E b = 1.401 eV). Interestingly, HBTD9 manifested to be the prime candidate for non-fullerene organic solar cells (NF–OSCs) owing to the lowest energy band gap, large mobility of charges, and least value of binding energy while holding an excellent redshift value compared to all the designed chromophores. This study revealed that these chromophores would be potential competitors in manufacturing effective optoelectronic materials. • Designing of acridine based donor materials (HBTD2 - HBTD9) from HBTR1 via efficient acceptors. • Study of photovoltaic properties of aforesaid compounds through DFT. • Investigation of opto-electronic properties at B3LYP/6-311G(d,p) functional of DFT. • Efficacy of designed compounds was explored by investigating open circuit voltage. [ABSTRACT FROM AUTHOR]

Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry out the N 1 -substitution of 2,3-dihydroquinazolin-4(1 H )-one core. A set of 32 N-alkylated/benzylated quinazoline derivatives were synthesized, characterized and evaluated for their inhibition against cholinesterases. N-alkylation of the series of the compounds reported previously (N-unsubstituted) resulted in improved activity. All the compounds showed inhibition of both enzymes in the micromolar to submicromolar range. Structure activity relationship (SAR) of the 32 derivatives showed that N-benzylated compounds possess good activity than N-alkylated compounds. N-benzylated compounds 2ad and 2af were found very active with their IC 50 values toward AChE in submicromolar range (0.8 µM and 0.6 µM respectively). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational predictions of ADMET studies reveal that all the compounds have good pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover, all the compounds are predicted to be absorbed in human intestine and also have the ability to cross blood brain barrier. Overall, the synthesized compounds have established a structural foundation for the design of new inhibitors of cholinesterase. [ABSTRACT FROM AUTHOR]

In search of potent inhibitors of cholinesterases, we have synthesized and evaluate a number of 2,3-dihydroquinazolin-4(1H)-one derivatives. The synthetic approach provided an efficient synthesis of the target molecules with excellent yield. All the tested compounds showed activity against both the enzymes in micromolar range. In many case, the inhibition of both enzymes are higher than or comparable to the standard drug galatamine. With the selectivity index of 2.3 for AChE, compound 5f can be considered as a potential lead compound with a feature of dual AChE/BChE inhibition with IC 50 = 1.6 ± 0.10 μM (AChE) and 3.7 ± 0.18 μM (BChE). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. The computed binding modes of these compounds in the active site of AChE and BChE provide an insight into the mechanism of inhibition of these two enzyme. [ABSTRACT FROM AUTHOR]

The screening of hair follicles, dermal papilla cells, and keratinocytes through in vitro , in vivo , and histology has previously been reported to combat alopecia. Ficus benghalensis has been used conventionally to cure skin and hair disorders, although its effect on 5 α -reductase II is still unknown. Currently, we aim to analyze the phytotherapeutic impact of F. benghalensis leaf extracts (FBLEs) for promoting hair growth in rabbits along with in vitro inhibition of the steroid isozyme 5 α -reductase II. The inhibition of 5 α -reductase II by FBLEs was assessed by RP-HPLC, using the NADPH cofactor as the reaction initiator and Minoxin (5%) as a positive control. In silico studies were performed using AutoDock Vina to visualize the interaction between 5 α -reductase II and the reported phytoconstituents present in FBLEs. Hair growth in female albino rabbits was investigated by applying an oral dose of the FBLE formulation and control drug to the skin once a day. The skin tissues were examined by histology to see hair follicles. Further, FAAS, FTIR, and antioxidants were performed to check the trace elements and secondary metabolites in the FBLEs. The results of RP-HPLC and the binding energies showed that FBLEs reduced the catalytic activity of 5 α -reductase II and improved cell proliferation in rabbits. The statistical analysis ( p < 0.05 or 0.01) and percentage inhibition (>70%) suggested that hydroalcoholic FBLE has more potential in increasing hair growth by elongating hair follicle's anagen phase. FAAS, FTIR, and antioxidant experiments revealed sufficient concentrations of Zn, Cu, K, and Fe, together with the presence of polyphenols and scavenging activity in FBLE. Overall, we found that FBLEs are potent in stimulating hair follicle maturation by reducing the 5 α -reductase II action, so they may serve as a principal choice in de novo drug designing to treat hair loss., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Iltaf, Noreen, Rehman, Ghumman, Batool, Mehdi, Hasan, Ijaz, Akram and Butt.)

The photonic structure of cut muscle tissues reveals that the well-ordered gratings diffract light, producing iridescent colours. Cut fibrils protruding from the muscle surface create a two-dimensional periodic array, which diffract light at specific wavelengths upon illumination. However, this photonic effect misleads consumers in a negative way to relate the optical phenomenon with the quality of the product. Here we discuss the fundamentals of this optical phenomenon and demonstrate a methodology for quantitatively measuring iridescence caused by diffraction gratings of muscle tissue surface of pork ( Sus scrofa domesticus ) using reflection spectrophotometry. Iridescence was discussed theoretically as a light phenomenon and spectral measurements were taken from the gratings and monitored in real time during controlled drying. The findings show that the intensity of diffraction diminishes as the surface grating was dried with an air flow at 50 °C for 2 min while the diffracted light wavelength was at 585 ± 9 nm. Our findings indicate that the diffraction may be caused by a blazed surface grating. The implications of the study include providing guidelines to minimise the iridescence by altering the surface microstructure, and in consequence, removing the optical effect.