Design, synthesis, in-vitro thymidine phosphorylase inhibition, in-vivo antiangiogenic and in-silico studies of C-6 substituted dihydropyrimidines.

Thymidine phosphorylase (TP) is an angiogenic enzyme. It plays an important role in angiogenesis, tumour growth, invasion and metastasis. In current research work, we study the effect of structural modification of dihydropyrimidine-2-ones (DHPM-2-ones) on TP inhibition. A series of eighteen new derivatives of 3,4-dihydropyrimidone-2-one were designed and synthesized through the structural modification at C-6 position. All these new derivatives were then assessed for in-vitro inhibition of thymidine phosphorylase (TP) from E. coli. Oxadiazole derivatives 4a-e exhibited excellent TP-inhibition at low micromolar concentration levels better than standard drug 7-deazaxanthine (7-DX). Among all these compounds, 4b was found to be the most potent with IC50 = 1.09 ±â€¯0.004 µM. Anti-angiogenesis potential of representative compounds were also studied in a chorioallantoic membrane (CAM) assay. Here again, compound 4b was found to be the potent anti-angiogenesis compound in a CAM assay. Docking studies were also performed with Molecular Operating Environment (MOE) to further analyse the mode of inhibition of these compounds. Binding mode analysis of the most active inhibitors showed that these are well accommodated into the binding site of enzyme though stable hydrogen bonding and hydrophobic interactions.

Design, synthesis, in vitro Evaluation and docking studies on dihydropyrimidine-based urease inhibitors.

In our previous report, we have identified 3,4-dihydropyrimidine scaffold as promising class of urease inhibitor in a structure based virtual screen (SBVS) experiment. In present study, we attempted to optimize the scaffold by varying C-5 substituent. The elongation of the C-5 chain was achieved by the reaction of C-5 ester with hydrazine leading to C-5 carbohydrazides which were further used as building blocks for the synthesis of fifteen new compounds having diverse moieties. A significantly higher in vitro urease inhibitory activity with IC50 values in submicromolar range was observed for semithiocarbazide derivatives (4a-c, 0.58-0.79µM) and isatin Schiff base derivative 5a (0.23µM). Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its key amino acid residues. The overall results of urease inhibition have shown that these compounds can be further optimized and developed as lead urease inhibitors.

Synthesis, in vitro and computational studies of 1,4-disubstituted 1,2,3-triazoles as potential α-glucosidase inhibitors.

1,4-Disubstituted-1,2,3-triazoles were synthesized by Cu(I) catalyzed click reaction, where the azides, with electron donating and electron withdrawing groups acted as 1,3-dipoles and 1-ethynyl-1-cyclohexanol served as the terminal alkyne. These synthesized triazoles were subjected to enzymatic assay which showed promising activity against α-glucosidase; 1-(2-cyano-4-nitrophenyl)-4-(1-hydroxycyclohexyl)-1H-1,2,3-triazole 3m being the most active members of the library. Molecular docking studies of these triazoles with the homology-modeled α-glucosidase protein were also performed to delineate ligand-protein interactions at molecular level which suggested that Phe157, Arg312 and His279 are the major interacting residues in the biding site of the protein and may have a significant role in the inhibition of enzyme's function.

Analysis of severely fractured glenoid components: clinical consequences of biomechanics, design, and materials selection on implant performance.

BACKGROUND: The longevity of total shoulder replacement is primarily limited by the performance of the ultrahigh-molecular-weight polyethylene (UHMWPE) glenoid component in vivo. Variations in glenoid design (conformity, thickness), biomechanics (joint kinematics), and UHMWPE material selection (sterilization, cross-linking) distinguish total shoulder replacements from hip and knee arthroplasty devices. These variables can lead to severe mechanical failures, including gross fracture. METHODS: Sixteen retrieved glenoids with severe fracture were analyzed. The explant cohort included 3 material groups (gamma-sterilized Hylamer; gamma-sterilized UHMWPE; and gas plasma-sterilized, remelted, highly cross-linked UHMWPE [HXL]) and a range of conformities (0- to 10-mm radial mismatch). Analysis included fractography (optical and scanning electron microscopy) and Fourier transform infrared spectroscopy for oxidative analysis. RESULTS: Fracture primarily occurred along the exterior rim for all 16 explants. Fourier transform infrared analysis and fractography revealed significant oxidative embrittlement for all gamma-sterilized glenoids. Fatigue striations and internal flaws were evident on the fracture surface of the HXL glenoid, with little oxidation detected. CONCLUSIONS: Fracture initiated at the external rim of all devices. Elevated oxidation levels and visible material distortion for representative gamma-sterilized conventional and Hylamer devices suggest oxidative embrittlement as a driving force for crack inception and subsequent fracture. Brittle fracture of theHXL glenoid resulted from a combination of elevated contact stress due to a nonconforming surface, an internal flaw, and reduced resistance to fatigue crack growth. This demonstrates that glenoid fracture associated with oxidation has not been eliminated with the advent of modern materials (HXL) in the shoulder domain. LEVEL OF EVIDENCE: Basic Science Study; Implant Retrieval Study.

Therapeutic potential of clinically proven natural products in the management of dementia.

Dementia is a common neurodegenerative disorder connected to damage to nerve cells in the brain. Although some conventional drugs are available for dementia treatments and are still sanctified for dementia patients, their short- and long-term side effects and other limitations make treating patients more challenging. The authors aimed to explain novel options for treating dementia with natural products and unravel some clinically proven natural products. This article systematically reviewed recent studies that have investigated the role of natural products and their bioactive compounds for dementia. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter.In this review, we provide mechanistic insights of clinically validated natural products, including like- Yokukansan, Souvenaid, BDW, Hupergene, Bacopa monnier, Omega-3, Tramiprostate and Palmitoylethanolamide with which have therapeutic efficacy against dementia in the management of dementia. As shown by studies, certain natural ingredients could be used to treat and prevent dementia. We strongly believe that the medicinal plants and phytoconstituents alone or in combination with other compounds would be effective treatments against dementia with lesser side effects as compared to currently available treatments. Moreover, these products should be studied further in order to develop novel dementia medications.

Design considerations for studies of the biomechanical environment of the femoropopliteal arteries.

OBJECTIVE: The purpose of this study was to review the available literature regarding the biomechanics of the superficial femoral artery (SFA) and popliteal artery (PA) in patients with peripheral arterial disease (PAD). Stents are one of many available therapies used to treat patients with PAD. Because stents are permanent implants, they undergo a variety of deformations as patients go about their daily activities such as walking, sitting in a chair, or climbing stairs. As a part of the marketing application for United States Food and Drug Administration approval, stents need to be evaluated for long-term durability under a variety of loading modes. The information available in the literature provides direction for such evaluation. METHODS: We performed a literature search of the PubMed database looking for "key vessel" and "mechanics" (all fields) or "deformation" (all fields) or "flexion" (all fields) or "mechanical environment" (all fields) or "tortuosity" (all fields) or "dynamics" (all fields) or "forces" (all fields), where the "key vessel" was "Femoral Artery," "Superficial Femoral Artery," "Popliteal Artery," and "Femoropopliteal." RESULTS: Using a decision tree, we found 12 relevant articles that focused solely on the nonradial cyclic deformations associated with musculoskeletal motion. Despite the many limitations associated with combining these studies, we learned that under walking conditions, the proximal and mid-SFA deforms, on average, by shortening in the axial direction 4.0%, by twisting 2.1°/cm, and by bending 72.1 mm; the distal SFA and proximal PA deform by shortening in the axial direction 13.9%, by twisting 3.5°/cm, and by being pinched such that the aspect ratio of the lumen changes 4.6%. The distal PA deforms by shortening in the axial direction 12.3%, by twisting 3.5°/cm, by bending 22.1 mm, and by being pinched such that the aspect ratio of the lumen changes 12.5%. CONCLUSIONS: A review of the current literature reveals heterogeneous study designs that confound interpretation. Studies included different physiologic settings from young to mature participants, participants with and without disease, and cadavers. Investigators used a range of imaging modalities and definitions of arterial segments, which affected our ability to compile the data as we learned that deformations vary according to the specific anatomic location within the SFA/PA. As a result of this analysis, we identified design considerations for future studies, because although this work has been valuable and significant, there are many limitations with the currently available data such that all we know about the SFA/PA environment is that we don't know.

Brine shrimp lethality assay 'an effective prescreen': microwave-assisted synthesis, BSL toxicity and 3DQSAR studies-based designing, docking and antitumor evaluation of potent chalcones.

CONTEXT: In the course of searching potential antitumor agents from a library of chalcones synthesized under microwave irradiations, the brine shrimp lethality (BSL) assay and a 3D structure-activity relationship (3DQSAR) studies were followed by the antitumor evaluation of most potent analogues. OBJECTIVE: The objective of the current study was to effectively use the BSL assay for the identification of potential cytotoxic analogues from a set of compounds. METHODS: We applied the comparative molecular field analysis (CoMFA) and devised 3DQSAR on 33 synthesized chalcones leading to prediction of five related compounds with improved activity. The scope of BSL assay for the prediction of antitumor potency was tested through the in vitro antitumor studies against six human tumor cell-lines, docking studies and the tubulin-polymerization assay. RESULTS: The newly designed compounds 34-38 displayed very promising cytotoxic potency. From our results, the BSL toxicity, antitumor efficacy and docking outcomes could be easily co-related. CONCLUSION: The study draws a very good relationship between a simple, inexpensive, and bench-top BSL assay and the antitumor potential of the cytotoxic compounds. Devising the CoMFA analysis helped in designing chalcones with improved cytotoxic potential as displayed through their BSL and cytotoxic activity against human tumor cell lines. The studies are noteworthy as such comprehensive studies were never performed before on the BSL assay. The present studies widen the scope of the BSL model that may prove quite helpful as a preliminary screen in the antitumor drug designing and synthesis expeditions.

Synthesis, in vitro antibacterial and antifungal activity of some n-acetylated and non-acetylated pyrazolines.

Fourteen new N-acetylated and non-acetylated pyrazoline derivatives were synthesized by reacting chalcones with hydrazine in the presence of absolute ethanol however reaction was carried out in the presence of glacial acetic acid to afford N-acetylated pyrazolines. The chemical structures of the synthesized pyrazolines were confirmed by FTIR, (1)HNMR, (13)CNMR and mass spectroscopic data. The pyrazolines (1-14) were screened for antibacterial activity against ten bacterial strains using seven Gram-positive and three Gram-negative bacteria and antifungal activity against Aspergillus flavus, Aspergillus niger and Aspergillus pterus. Pyrazolines (1-14) found to exhibit good to excellent antimicrobial activities compared to the levofloxacin and fluconazole used as standard drugs.

Myths, misconceptions and attitudinal trends among patients with acne.

Background Despite acne being a common dermatological problem, there is a paucity of literature addressing the knowledge, attitude and practice about it. Aims/Objectives To find out what patients know about acne, its cause and treatment, as well as myths, misconceptions and attitude towards it. Methods A cross-sectional, descriptive questionnaire-based study on acne patients at Maharana Bhupal Hospital, RNT Medical College, Udaipur, Rajasthan, India. Results Most (84.8%) patients belonged to the age group of 16-25 years. The majority (63.9%) presented 12 months after the onset of acne. More than half had average knowledge, a positive attitude and good practices, related significantly to gender and education. Limitations A standardized questionnaire suitable for all dialects and regional languages would have yielded more uniform results. Conclusion Study revealed that acne patients still need to acquire accurate, adequate and easily accessible information to seek timely and appropriate treatment, and alleviate their psychological suffering.

Morphological Patterns of Balanoposthitis and their Correlation with Final Etiological Diagnosis.

Background: Balanoposthitis is a common dermatological condition across the globe, but studies describing clinico-morphologic features and their diagnostic correlates are scarce. Objective: To study various morphological patterns of balanoposthitis and their correlation with etiological diagnosis. Materials and Methods: A cross-sectional study was conducted on all patients with balanoposthitis visiting the dermatology out-patient department and sexually transmitted disease (STD) clinic over a period of 8 months. Detailed history, demographic data, and clinical features were recorded. Relevant investigations were performed. Results: A total of 129 patients of balanoposthitis were studied. Common causes were because of candida (33.3%), bacteria (17.1%), irritants (13.3%), herpes (11.4%), drugs (8.6%), and lichen sclerosus (6.7%). Common morphological patterns were erosion/confluent wet erythema with sub-preputial discharge (24.81%), fissure with superficial pustules (15.5%), fissure alone (13.18%), patchy dry erythema (11.63%), and superficial pustules (intact or exfoliated) with or without underlying erythema (10.85%). Fissure and superficial pustules were the most common presentation of candidal balanoposthitis (51.43%), erosions/confluent wet erythema with sub-preputial discharge of bacterial balanitis (55.56%), and patchy dry erythema of irritant balanitis (50%). Limitations: Detailed investigations such as fungal culture, herpes serology, real-time polymerase chain reaction and histopathology could not be performed. Conclusion: Certain morphological patterns of balanoposthitis strongly point toward final diagnosis which can help in quick diagnosis and early treatment in resource poor settings, especially in STDs.

Clinical triad with multi-biopsy histopathology as a reliable diagnostic marker of mycetomas: a retrospective review from a tertiary care center.

BACKGROUND: Mycetoma is a neglected tropical infectious disease which runs a prolonged and protracted course. Microbiological confirmation is diagnostic yet unreliable due to poor sensitivity and variable availability of culture facilities in resource poor settings. METHODS: A retrospective review was performed on electronic records (histopathology, microbiology, and radiology) of all patients who underwent skin biopsies with mycetoma as one of the clinical differential diagnoses from year 2016 to 2020. RESULTS: Out of 73 patients biopsied with a differential of mycetoma, 42 fit the clinical triad of swelling-sinuses-granules. After clinical, microbiological, pathological, and radiological correlation, 31 cases were of eumycetoma and seven were of actinomycetoma. Mean patient age was 37.58 ± 13.8 years with a male to female ratio 2.45 : 1 and mean disease duration of 11.31 ± 10.9 years. Histopathological findings revealed fungal hyphae in 18 cases and gram-positive bacteria in six cases. Fungal culture was positive in 13 cases with the three commonest organisms being Madurella mycetomatis in five cases, Fusarium and Aspergillus nidulans in two cases each. X-ray changes of soft tissue, bones, and joints were seen in 25 cases, and "dot-in-circle" sign was seen in eight of nine MRIs. CONCLUSION: Eumycetoma was more common than actinomycetoma in our setup, ratio being 4.43 : 1. A clinical triad of swelling, multiple sinuses and grainy discharge with any one diagnostic support (histopathology/radiology) is sufficient to make a definitive diagnosis of mycetoma in the absence of microbiological identification.

A comprehensive review on clinically proven natural products in the management of nerve pain, with mechanistic insights.

Introduction: People are treating their neuropathic pain with several approved and licensed pharmacological drugs. But due to having existing limitations like low efficacy with some side effects, there needs to be a more effective alternative and complementary therapeutic options. Purpose: s: The study was designed to discuss the mechanistic role of several clinically proven natural products that have been shown to play a significant role against different nerve pain or neuropathic pain. Method: ology: Information for this review article was salvaged using several accessible searching databases like SciVerse Scopus ® (Elsevier Properties S. A, USA), Web of Science® (Thomson Reuters, USA), and PubMed® (U.S. National Library of Medicine, USA) considering some search items like - nerve pain, natural products in pain/nerve pain management, clinically proven natural products in pain management, pain-reducing agents and so on. Result: Our study reported the therapeutic efficacy of natural products and their possible mechanism against neuropathic pain in the human body. Natural products widely used to treat neuropathic pain include comfrey root extract ointment, lavender oil, Rose Oil, aromatic essential oil, ginger oil, vitex agnus-castus, peganum oil, and ajwain 10%. Some common pathways are involved in pain relief through sensory stimulation, enzymatic, anti-inflammatory, and pain-related receptor regulation. Conclusion: The present study suggests that the mentioned natural products can be an appropriate choice for the treatment and management of neuropathic pain.

A comprehensive review on clinically proven medicinal plants in the treatment of overweight and obesity, with mechanistic insights.

Background and objectives: Obesity has become a global health issue, more precisely, a pandemic throughout the present world due to its high prevalence in the recent era. Increased risk of morbidity and mortality in obese patients can be attributed to its association with the development of different life-threatening conditions. Plants are considered one of the most important sources of bioactive molecules which are used against a wide range of health disorders. This systematic review explores the efficacy as well as the safety profile of commonly used medicinal plants in the management of obesity that may help people to maintain a healthy weight. Methods: This review is based on comprehensive literature searches from PubMed, Science Direct, Scopus, and Google Scholar databases using the keywords- "plants in obesity", "plants used in weight reduction" or keywords that are similar to those. Medicinal plants which have been clinically proven for their anti-obesity effect have only been selected for this study and attempts to investigate beneficial effects and adverse effects along with their mechanism of action have also been taken in this review. Results: A significant reduction of weight in both human and other animals are exhibited by the extracts of Phaseolus vulgaris, green coffee, Yerba Mate, green tea, Gynostemma pentaphyllum, and the combination of Cissus quadrangularis/Irvingia gabonensis. All of those plant extracts seemed to work on different physiological pathways and none of those extracts showed any notable adverse effects in human or animal models. Conclusion: Our review suggests that the discussed medicinal plants are effective in reducing the weight of obese patients without causing notable adverse reactions. Although further study is necessary to confirm their exact molecular mechanism and safety in human use.

Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics.

The chemical similarity of antibacterial cyclic peptides and peptidomimetics was studied in order to identify new promising cyclic scaffolds. A large descriptor space coupled with cluster analysis was employed to digitize known antibacterial structures and to gauge the potential of new peptidomimetic macrocycles, which were conveniently synthesized by acylbenzotriazole methodology. Some of the synthesized compounds were tested against an array of microorganisms and showed antibacterial activity against Bordetella bronchistepica, Micrococcus luteus, and Salmonella typhimurium.

Extensive actinomycosis with intracranial and mediastinal involvement: a therapeutic challenge.

Central nervous system (CNS) involvement by actinomycosis is rare, seen in 2%-3% cases. It mostly spreads to CNS by haematogenous route from a distant primary site such as oral cavity, lung, abdomen or pelvis. Direct CNS extension can also occur. It mostly presents as brain abscess, meningoencephalitis, actinomycetoma, subdural empyema and epidural abscess. We report one case of extensive actinomycosis having intra and extraparenchymal CNS, spinal canal, retropharyngeal and mediastinal involvement. Due to such widespread extension and involvement of vital areas, complete surgical debulking was not possible. In addition to therapeutic resistance to conventional antibiotics, repetitive negative cultures posed significant difficulty in the case management.

Synthesis, characterization, anti-inflammatory and in vitro antimicrobial activity of some novel alkyl/aryl substituted tertiary alcohols.

The synthesis of some novel alkyl/aryl substituted tertiary alcohols was accomplished in two steps. The synthetic route involves preparation of Grignard reagents by treating alkyl/aryl bromides with magnesium turnings in dry ether. Then substituted chalcones were reacted with the Grignard reagents to afford alkyl/aryl substituted tertiary alcohols 1-10. The structures of the synthesized compounds were assigned on the basis of FT-IR, 1H-NMR, 13C-NMR and mass spectroscopic data. The in vivo anti-inflammatory activity of the synthesized compounds was evaluated using the carrageenan-induced hind paw edema method and was compared with that of ibuprofen. Some of the newly synthesized compounds showed promising anti-inflammatory activity. The tertiary alcohols 1-10 were also screened for antibacterial activity against ten bacterial strains using seven Gram-positive and three Gram-negative bacteria and for antifungal activity against Aspergillus Flavus, Aspergillus Niger and Aspergillus pterus. Tertiary alcohols 1-10 were found to exhibit good to excellent antimicrobial activities compared to levofloxacin and fluconazole used as standard drugs.

In silico modeling of the specific inhibitory potential of thiophene-2,3-dihydro-1,5-benzothiazepine against BChE in the formation of beta-amyloid plaques associated with Alzheimer's disease.

BACKGROUND: Alzheimer's disease, known to be associated with the gradual loss of memory, is characterized by low concentration of acetylcholine in the hippocampus and cortex part of the brain. Inhibition of acetylcholinesterase has successfully been used as a drug target to treat Alzheimer's disease but drug resistance shown by butyrylcholinesterase remains a matter of concern in treating Alzheimer's disease. Apart from the many other reasons for Alzheimer's disease, its association with the genesis of fibrils by beta-amyloid plaques is closely related to the increased activity of butyrylcholinesterase. Although few data are available on the inhibition of butyrylcholinesterase, studies have shown that that butyrylcholinesterase is a genetically validated drug target and its selective inhibition reduces the formation of beta-amyloid plaques. RATIONALE: We previously reported the inhibition of cholinesterases by 2,3-dihydro-1, 5-benzothiazepines, and considered this class of compounds as promising inhibitors for the cure of Alzheimer's disease. One compound from the same series, when substituted with a hydroxy group at C-3 in ring A and 2-thienyl moiety as ring B, showed greater activity against butyrylcholinesterase than to acetylcholinesterase. To provide insight into the binding mode of this compound (Compound A), molecular docking in combination with molecular dynamics simulation of 5000 ps in an explicit solvent system was carried out for both cholinesterases. CONCLUSION: Molecular docking studies revealed that the potential of Compound A to inhibit cholinesterases was attributable to the cumulative effects of strong hydrogen bonds, cationic-pi, pi-pi interactions and hydrophobic interactions. A comparison of the docking results of Compound A against both cholinesterases showed that amino acid residues in different sub-sites were engaged to stabilize the docked complex. The relatively high affinity of Compound A for butyrylcholinesterase was due to the additional hydrophobic interaction between the 2-thiophene moiety of Compound A and Ile69. The involvement of one catalytic triad residue (His438) of butyrylcholinesterase with the 3'-hydroxy group on ring A increases the selectivity of Compound A. C-C bond rotation around ring A also stabilizes and enhances the interaction of Compound A with butyrylcholinesterase. Furthermore, the classical network of hydrogen bonding interactions as formed by the catalytic triad of butyrylcholinesterase is disturbed by Compound A. This study may open a new avenue for structure-based drug design for Alzheimer's disease by considering the 3D-pharmacophoric features of the complex responsible for discriminating these two closely-related cholinesterases.

Investigation of redox mechanism and DNA binding of novel 2-(x-nitrophenyl)-5-nitrobenzimidazole (x = 2, 3 and 4).

The present study describes the investigation of the binding modes of potential anti-cancerous nitrophenyl derivatives of 2-(x-nitrophenyl)-5-nitrobenzimidazole with calf thymus DNA. The -2-(x-nitrophenyl)-5-nitrobenzimidazoles under investigation differ only in position x of nitro group in nitrophenyl substituent relative to benzimidazole moiety leading to 1-NPNB (x = 2), 2-NPNB (x = 3) and 3-NPNB (x = 4). The DFT calculations predicted that derivatives were electrochemically reducible which was then confirmed by cyclic voltammetry. In cyclic voltammetry, the second reversible peak was dependent on first irreversible reduction. This revealed that electrochemical irreversible process was governed by some other process which was then followed by reversible second electron transfer. Thus, ECE (electron transfer leading to coupled chemical reaction followed by another electron transfer process) mechanism was attributed for electrochemical reduction. Experimental results based on UV-Vis spectroscopy vaguely showed intercalation of 1-NPNB, 2-NPNB and 3-NPNB into DNA which was assisted by cyclic voltammetry. However, thermal melting and florescence spectroscopy unambiguously established intercalation for all three compounds. Molecular docking analysis ascertained in pocket stacking of 5-nitrobenzimidazole moiety in 1-NPNB and 2-NPNB while nitro phenyl substitution in 3-NPNB stacks between DNA base pair during intercalation which was in agreement with DFT computed molecular geometry. Therefore, the relative positions of nitro group and 5-nitrobenzimidazole moieties in 2-(x-nitrophenyl)- 5-nitrobenzimidazole influenced the DNA binding pattern of compounds during intercalation. The cytotoxicity of these compounds was comparable to standard drug doxorubicin against both cancerous (MCF-7) and normal (MCF-10A) breast cells which depicts their anti-cancerous potential.

In silico studies of urease inhibitors to explore ligand-enzyme interactions.

In continuation of our previous study on the urease inhibition by a number of chalcones, 2,3-dihydro-1,5-benzothiazepines and 2,3,4,5-tetrahydro-1,5-benzothiazepines, FlexX docking has been exploited to get a deeper insight into the mechanism of their inhibitory action. A comparison of the IC(50) values of the active compounds reveals that, of the three classes of compounds studied, 2,3-dihydro-1,5-benzothiazepines were the most potent urease inhibitors. An in silico examination of these compounds showed that the activity is related to the interaction of ligand with the nickel metallocentre, its interaction with two amino acid residues, Asp224 and Cys322, in addition to the orientation of rings A and B in the catalytic core of the enzyme. The most active compound 2,3-dihydro-1,5-benzothiazepine (4) anchor tightly through a network of interactions with Ni701 and Ni702. This includes a number of hydrogen bonds and hydrophobic contacts with the amino acid residues in its vicinity. For their reduced analogs, the difference in the activity of different diastereomers has been observed to be configuration-dependent. This may be ascribed mainly to the difference in the orientation of ring B of the two stereoisomers and the extent of their interaction with Asp224 and Cys322 present in the catalytic core of the enzyme.