Reverse or inverse docking is proving to be a powerful tool for drug repositioning and drug rescue. It involves docking a small-molecule drug/ligand in the potential binding cavities of a set of clinically relevant macromolecular targets. Detailed analyses of the binding characteristics lead to ranking of the targets according to the tightness of binding. This process can potentially identify novel molecular targets for the drug/ligand which may be relevant for its mechanism of action and/or side effect profile. Another potential application of reverse docking is during the lead discovery and optimization stages of the drug-discovery cycle. This review summarizes the state-of-the-art and future prospects of the reverse docking with particular emphasis on computational molecular design.

Nanocrystalline cellulose (NCC) has gained attention due to its versatile properties such as biocompatibility, sustainability, high aspect ratio, and abundance of -OH groups that favor modifications of NCC. The objective of this paper is to develop NCC by extracting and characterizing NCC prepared from banana peel powder (BPP). BPP was subjected to alkali and bleaching treatment to remove lignin and hemicellulose and then subjected to acid hydrolysis to prepare NCC. Under optimal conditions (200 mL of sulfuric acid 55% v/v at 50 °C for 60 min), the NCC yield was found to be 29.9%. The particle size and zeta potential of the NCC were found to be 209 nm and -43 mV, respectively. Attenuated total reflectance Fourier transform infrared spectroscopy showed successful removal of lignin and hemicellulose from BPP after the alkali treatment, bleaching, and acid hydrolysis. Field emission scanning electron microscopy showed needle-shaped crystals and transmission electron microscopy showed particles in the nano range. X-ray diffraction analysis showed that the crystallinity index of NCC was 64.12% while keeping the cellulose I crystal structure intact. Thermogravimetric analysis showed good stability which paves way for NCC to be explored for various applications. All the parameters evaluated indicated that NCC was successfully prepared from BPP using alkali treatment, bleaching, and acid hydrolysis.

A major global health risk has been witnessed with the development of drug-resistant bacteria and multidrug-resistant pathogens linked to significant mortality. Coumarins are heterocyclic compounds belonging to the benzophenone class enriched in different plants. Coumarins and their derivatives have a wide range of biological activity, including antibacterial, anticoagulant, antioxidant, anti-inflammatory, antiviral, antitumour, and enzyme inhibitory effects. In the past few years, attempts have been reported towards the optimization, synthesis, and evaluation of novel coumarin analogues as antimicrobial agents. Several coumarin-based antibiotic hybrids have been developed, and the majority of them were reported to exhibit potential antibacterial effects. In the present work, studies reported from 2016 to 2020 about antimicrobial coumarin analogues are the focus. The diverse biological spectrum of coumarins can be attributed to their free radical scavenging abilities. In addition to various synthetic strategies developed, some of the structural features include a heterocyclic ring with electron-withdrawing/donating groups conjugated with the coumarin nucleus. The suggested structure−activity relationship (SAR) can provide insight into how coumarin hybrids can be rationally improved against multidrug-resistant bacteria. The present work demonstrates molecular insights for coumarin derivatives having antimicrobial properties from the recent past. The detailed SAR outcomes will benefit towards leading optimization during the discovery and development of novel antimicrobial therapeutics.

The widely abused psychostimulant cocaine is thought to elicit its reinforcing effects primarily via inhibition of the neuronal dopamine transporter (DAT). However, not all DAT inhibitors share cocaine’s behavioral profile, despite similar or greater affinity for the DAT. This may be due to differential molecular interactions with the DAT. Our previous work using transporter mutants with altered conformational equilibrium (W84L and D313N) indicated that benztropine and GBR12909 interact with the DAT in a different manner than cocaine. Here, we expand upon these previous findings, studying a number of structurally different DAT inhibitors for their ability to inhibit [³H]CFT binding to wild‐type, W84L and D313N transporters. We systematically tested structural intermediates between cocaine and benztropine, structural hybrids of benztropine and GBR12909 and a number of other structurally heterologous inhibitors. Derivatives of the stimulant desoxypipradrol (2‐benzhydrylpiperidine) exhibited a cocaine‐like binding profile with respect to mutation, whereas compounds possessing the diphenylmethoxy moiety of benztropine and GBR12909 were dissimilar to cocaine‐like compounds. In tests with specific isomers of cocaine and tropane analogues, compounds with 3α stereochemistry tended to exhibit benztropine‐like binding, whereas those with 3β stereochemistry were more cocaine‐like. Our results point to the importance of specific molecular features – most notably the presence of a diphenylmethoxy moiety – in determining a compound’s binding profile. This study furthers the concept of using DAT mutants to differentiate cocaine‐like inhibitors from atypical inhibitors in vitro. Further studies of the molecular features that define inhibitor–transporter interaction could lead to the development of DAT inhibitors with differential clinical utility.