2D-QSAR STUDY ON SOME NOVEL DIHYDROPYRIMIDINE-4-CARBONITRILE ANALOGS AS AN ANTIFUNGAL ACTIVITY Original Article RIDDHI PATEL 1* , T. Y. PASHA 2 , SANDIP PATEL 1 1 N. R. Vekaria institute of Pharmacy, Junagadh, Gujarat, India, 2 Sri Adichunchanagiri College of Pharmacy, B G Nagara, Nagamangala Taluk Mandya, Karnataka, 571448, India Email: riddhi.mdh@gmail.com Received: 07 Dec 2022, Revised and Accepted: 24 Jan 2023 ABSTRACT Objective: The present study was designed to study the antifungal activity of Dihydropyrimidine-4-Carbonitrile analogs against the fungi Candida albicans by a 2D quantitative structure-activity relationship (QSAR) model. Methods: The pyrimidine derivatives were produced using lipophilic, electronic, and steric parameters by Quantitative Structure Activity- Relationships (QSAR). A relationship between dependent and independent variables (biological activities and physicochemical descriptors, respectively) was resolved statistically using regression analysis. The F value shows the level of statistical significance of the regression (r 2 ) was used to report the fitness of data. The newly synthesized derivatives were evaluated for in vitro antifungal activity against Candida albicansby Nutrient agar and Seaboard dextrose agar media. Results: Multiple linear regression is a method of crucial importance, it allowed us to obtain a relation between the calculated parameters and the antifungal activity; this we can interpret the variance of the activity by contribution to the calculated descriptors. Quantitative structure-activity relationship (QSAR) model showing a significant activity-descriptors relationship accuracy of 90% (R 2 ≥ 0.90) and activity prediction accuracy of 81% (R²cv = 0.81). These values prove that the model obtained is reliable. Out of the three descriptors studied; log P has minimum potency, molar refractivity has more potency and heat of formation has moderate potency. Conclusion: Important structural understanding in the pattern of potent antifungal agents by Quantitative Structure Activity-Relationships (QSAR) study. The acquired physicochemical properties (electronic, topological, and steric) show the important structural features required for antifungal activity against Candida albicans. Keywords: 2D-QSAR, Antifungal agents, Dihydropyrimidine © 2023 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijpps.2023v15i3.47008. Journal homepage: https://innovareacademics.in/journals/index.php/ijpps. INTRODUCTION Some novel antifungal agents have been evaluated as a very important step for investigators. In general, the research programmed attempts are handled toward the design of new drugs because of the acquisition of resistance by the infecting organisms to present drugs and the unsatisfactory status of the present drug's side effects. Standard antibiotic resistance of common microorganisms is rapidly becoming a major health problem throughout the world [1, 2]. There is a real viewed need for the discovery of new derivatives provided with antifungal activity. The importance of organisms and treatment and methods of prevention differ with each group. Over a decade, the ubiquity of systemic fungal infections has increased significantly [3]. In the past 10 y, the use of broad-spectrum antibiotics used is increased, so the development of antifungal drugs has expanded, but there is still a deficiency in the range and scope of current antifungal properties. The modifications of existing drug molecules have been developed to improve activity and eliminate toxicity [4-6]. In short, antifungal activity has developed rapidly in the past few years analyzed to previous years, and the direction for the treatment of fungal infections is modified shortly soon as our knowledge of fungal infections enhance and new antifungal therapies are invented [7]. The quantitative structure-activity/property relationships (QSAR/QSPR) of substances are investigated by drug discovery, medicinal chemistry, biochemistry, and an important aspect of modern chemistry. The information acquired is made by mathematical equations relating the chemical structure of the derivatives to a huge variety of their physical, biological, chemical, and technological properties. Those not synthesized, yet those derivatives can readily be screened in silico for selection of structures with desired properties. Once a correlation between structure and activity/property is established, any number of derivatives. Hence, it is possible to select the most favorable derivatives for synthesis and testing in the laboratory [8, 9]. Theoretical drug designs have been most widely and effectively used in the analysis of quantitative structure-activity relationships (QSAR). This method has also been called the Hansch approach method and it supposes that the strength of a certain biological activity applied by a series of corresponding derivatives can be shown in terms of a function of various physical and chemical (electronic, hydrophobic, and steric) properties [10-12]. These purposes could be produced in a quantitative structure-activity relationships(QSAR)equation appearing certain effects approving for the antifungal activity, structural modifications that enhance various physical and chemical (electronic, hydrophobic, and steric) properties would be awaited to generate good active derivatives. MATERIALS AND METHODS Antifungal activity The newly synthesized derivatives were evaluated for in vitro antifungal activity against Candida albicans ATCC 10231(HIMEDIA). Nutrient agar and Seaboard dextrose agar were worked for fungal growth. The means of the standard twofold serial dilution method determined Minimal Inhibitory Concentrations (MIC) by using agar media. Stock solutions of tested derivatives were developed in Dimethyl sulfoxide (DMSO) at a concentration of 1 mg/ml. A Suspension containing around 106 CFUs/ml of fungi was arranged from broth cultures. Fungal plates were prepared in triplicate and incubated at 37 ᵒC within 48–72 h for fungi. Clotrimazole was also shown under the same conditions as an antifungal drug. MIC is explained as the minimum concentration of derivatives that inhibited visible growth [13]. International Journal of Pharmacy and Pharmaceutical Sciences Print ISSN: 2656-0097 | Online ISSN: 0975-1491 Vol 15, Issue 3, 2023